<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2023 Workiva-->
<!--r:65f08a08-e378-41c1-ae6e-1427f79ce66e,g:5cec771e-4778-4fc4-a658-2aed6390fb6b-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef roleURI="http://www.orasure.com/role/ConsolidatedBalanceSheets" xlink:type="simple" xlink:href="osur-20230630.xsd#ConsolidatedBalanceSheets"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/ConsolidatedBalanceSheets" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_c89c1f12-2ac5-475a-8bfd-3e6f36851c76" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_44f2917d-5515-4e5a-848a-247016603c20" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_c89c1f12-2ac5-475a-8bfd-3e6f36851c76" xlink:to="loc_us-gaap_LiabilitiesCurrent_44f2917d-5515-4e5a-848a-247016603c20" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesNoncurrent_b9bc1ea8-dfb5-405a-a0fb-768d2148b080" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LiabilitiesNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_c89c1f12-2ac5-475a-8bfd-3e6f36851c76" xlink:to="loc_us-gaap_LiabilitiesNoncurrent_b9bc1ea8-dfb5-405a-a0fb-768d2148b080" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_c5287dc9-116d-4ceb-9ff6-5b14e8100df2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_116c513a-704e-4817-8de3-adcddfb9d8a1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_c5287dc9-116d-4ceb-9ff6-5b14e8100df2" xlink:to="loc_us-gaap_AccountsPayableCurrent_116c513a-704e-4817-8de3-adcddfb9d8a1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_fe67c45f-793d-447d-902c-ac3fc06b72bd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_c5287dc9-116d-4ceb-9ff6-5b14e8100df2" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_fe67c45f-793d-447d-902c-ac3fc06b72bd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_osur_AccruedExpensesAndOtherCurrentLiabilities_57b74fd5-f380-4a69-abe3-497572f6e986" xlink:href="osur-20230630.xsd#osur_AccruedExpensesAndOtherCurrentLiabilities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_c5287dc9-116d-4ceb-9ff6-5b14e8100df2" xlink:to="loc_osur_AccruedExpensesAndOtherCurrentLiabilities_57b74fd5-f380-4a69-abe3-497572f6e986" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityCurrent_0c83cf16-eda3-4807-aee0-2b70c2925047" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinanceLeaseLiabilityCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_c5287dc9-116d-4ceb-9ff6-5b14e8100df2" xlink:to="loc_us-gaap_FinanceLeaseLiabilityCurrent_0c83cf16-eda3-4807-aee0-2b70c2925047" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_6f936f59-c5a8-4348-bb81-53d9ae5f2ca1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_c5287dc9-116d-4ceb-9ff6-5b14e8100df2" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_6f936f59-c5a8-4348-bb81-53d9ae5f2ca1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityCurrent_890f4e02-e777-4f13-957a-4557602eae79" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_c5287dc9-116d-4ceb-9ff6-5b14e8100df2" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityCurrent_890f4e02-e777-4f13-957a-4557602eae79" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_b0333574-0900-435b-af6a-4f35eca416b2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_87ee9e4f-d43c-4d49-9cf8-0d10a6c4f878" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_b0333574-0900-435b-af6a-4f35eca416b2" xlink:to="loc_us-gaap_Liabilities_87ee9e4f-d43c-4d49-9cf8-0d10a6c4f878" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_a5653ebb-88b1-46b9-96a9-f5839274fc58" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_b0333574-0900-435b-af6a-4f35eca416b2" xlink:to="loc_us-gaap_CommitmentsAndContingencies_a5653ebb-88b1-46b9-96a9-f5839274fc58" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_846fb0e2-c9c4-4f42-a8bd-19a9600698e6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_b0333574-0900-435b-af6a-4f35eca416b2" xlink:to="loc_us-gaap_StockholdersEquity_846fb0e2-c9c4-4f42-a8bd-19a9600698e6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_9fb06285-b31c-4e3c-a942-98965d2ec8bd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_fe389453-da3f-46bc-893c-227986aaadaf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PreferredStockValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_9fb06285-b31c-4e3c-a942-98965d2ec8bd" xlink:to="loc_us-gaap_PreferredStockValue_fe389453-da3f-46bc-893c-227986aaadaf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_f431c108-c785-46fe-b695-de90459ee78c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_9fb06285-b31c-4e3c-a942-98965d2ec8bd" xlink:to="loc_us-gaap_CommonStockValue_f431c108-c785-46fe-b695-de90459ee78c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalCommonStock_6a6f138b-78fe-49c7-88b7-2b4d85dd6170" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdditionalPaidInCapitalCommonStock"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_9fb06285-b31c-4e3c-a942-98965d2ec8bd" xlink:to="loc_us-gaap_AdditionalPaidInCapitalCommonStock_6a6f138b-78fe-49c7-88b7-2b4d85dd6170" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_9a4830e0-5eb9-49f6-9314-d4cbd94204ee" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_9fb06285-b31c-4e3c-a942-98965d2ec8bd" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_9a4830e0-5eb9-49f6-9314-d4cbd94204ee" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_1aea99dc-de00-4de4-91c0-863a1c3603da" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_9fb06285-b31c-4e3c-a942-98965d2ec8bd" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_1aea99dc-de00-4de4-91c0-863a1c3603da" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_3f5fa122-d2a2-402b-86c2-e7fe19cbc02c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_846e9283-0a72-4b0e-9ec5-1cf868e2a4dd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_3f5fa122-d2a2-402b-86c2-e7fe19cbc02c" xlink:to="loc_us-gaap_AssetsCurrent_846e9283-0a72-4b0e-9ec5-1cf868e2a4dd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsNoncurrent_00152ac0-ea45-45c8-bf35-4ab91fd133d8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_3f5fa122-d2a2-402b-86c2-e7fe19cbc02c" xlink:to="loc_us-gaap_AssetsNoncurrent_00152ac0-ea45-45c8-bf35-4ab91fd133d8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsNoncurrent_3dacdd2c-e675-4990-8963-d03f22787699" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsNoncurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_389fbe1c-3caf-4b9c-9eb4-cbdb0d12ef8b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsNoncurrent_3dacdd2c-e675-4990-8963-d03f22787699" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_389fbe1c-3caf-4b9c-9eb4-cbdb0d12ef8b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_9c011df1-7af9-45a3-881d-69bf00ca3af1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsNoncurrent_3dacdd2c-e675-4990-8963-d03f22787699" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_9c011df1-7af9-45a3-881d-69bf00ca3af1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseRightOfUseAsset_5ffa51fd-d49a-4c5e-8dfa-36277b49850f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinanceLeaseRightOfUseAsset"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsNoncurrent_3dacdd2c-e675-4990-8963-d03f22787699" xlink:to="loc_us-gaap_FinanceLeaseRightOfUseAsset_5ffa51fd-d49a-4c5e-8dfa-36277b49850f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_581c2776-431a-4808-8623-0daa100d487e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsNoncurrent_3dacdd2c-e675-4990-8963-d03f22787699" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_581c2776-431a-4808-8623-0daa100d487e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_e387b2f2-1f7c-4b63-b122-b60c86df975a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Goodwill"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsNoncurrent_3dacdd2c-e675-4990-8963-d03f22787699" xlink:to="loc_us-gaap_Goodwill_e387b2f2-1f7c-4b63-b122-b60c86df975a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_b53751e9-508d-42d5-b6c3-bad3a9010478" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsNoncurrent_3dacdd2c-e675-4990-8963-d03f22787699" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_b53751e9-508d-42d5-b6c3-bad3a9010478" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxAssetsNet_a53030eb-e43c-4a04-b222-64f9cacdb10e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredIncomeTaxAssetsNet"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsNoncurrent_3dacdd2c-e675-4990-8963-d03f22787699" xlink:to="loc_us-gaap_DeferredIncomeTaxAssetsNet_a53030eb-e43c-4a04-b222-64f9cacdb10e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesNoncurrent_87e5fbaa-2e41-4b09-aaf1-ba5d36f669d8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LiabilitiesNoncurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityNoncurrent_14425433-df05-40c2-a073-b19349dd45bf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinanceLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_87e5fbaa-2e41-4b09-aaf1-ba5d36f669d8" xlink:to="loc_us-gaap_FinanceLeaseLiabilityNoncurrent_14425433-df05-40c2-a073-b19349dd45bf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_0bce2150-4e33-48e3-a669-7abea1249a13" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_87e5fbaa-2e41-4b09-aaf1-ba5d36f669d8" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_0bce2150-4e33-48e3-a669-7abea1249a13" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent_adfbd9d8-9cd0-442a-8ffc-b322b8235f8e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_87e5fbaa-2e41-4b09-aaf1-ba5d36f669d8" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent_adfbd9d8-9cd0-442a-8ffc-b322b8235f8e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_b8ca8013-e7e9-43fe-95df-d4765d9a25f1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_87e5fbaa-2e41-4b09-aaf1-ba5d36f669d8" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_b8ca8013-e7e9-43fe-95df-d4765d9a25f1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxLiabilitiesNet_19f4b390-da3b-4ebb-9035-fe07b328b551" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredIncomeTaxLiabilitiesNet"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_87e5fbaa-2e41-4b09-aaf1-ba5d36f669d8" xlink:to="loc_us-gaap_DeferredIncomeTaxLiabilitiesNet_19f4b390-da3b-4ebb-9035-fe07b328b551" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_b94dbfb5-85ac-4f04-abba-b50d2c55c94c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_b8bed9d5-0cbb-4269-bee1-90cf9bf56ec4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_b94dbfb5-85ac-4f04-abba-b50d2c55c94c" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_b8bed9d5-0cbb-4269-bee1-90cf9bf56ec4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermInvestments_d88a6210-522b-4405-8d61-83d448fb3d38" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShortTermInvestments"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_b94dbfb5-85ac-4f04-abba-b50d2c55c94c" xlink:to="loc_us-gaap_ShortTermInvestments_d88a6210-522b-4405-8d61-83d448fb3d38" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_293d7b92-a74f-44bb-b162-d3248353a940" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_b94dbfb5-85ac-4f04-abba-b50d2c55c94c" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_293d7b92-a74f-44bb-b162-d3248353a940" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_8dec426f-3605-46f4-b61f-c069aa5605f9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InventoryNet"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_b94dbfb5-85ac-4f04-abba-b50d2c55c94c" xlink:to="loc_us-gaap_InventoryNet_8dec426f-3605-46f4-b61f-c069aa5605f9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseCurrent_28f40959-b214-4567-8768-b4eeb50b1ef4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PrepaidExpenseCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_b94dbfb5-85ac-4f04-abba-b50d2c55c94c" xlink:to="loc_us-gaap_PrepaidExpenseCurrent_28f40959-b214-4567-8768-b4eeb50b1ef4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsCurrent_429fe95b-d459-4fd4-986d-c6b10d05fab7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherAssetsCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_b94dbfb5-85ac-4f04-abba-b50d2c55c94c" xlink:to="loc_us-gaap_OtherAssetsCurrent_429fe95b-d459-4fd4-986d-c6b10d05fab7" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/ConsolidatedStatementsofOperations" xlink:type="simple" xlink:href="osur-20230630.xsd#ConsolidatedStatementsofOperations"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/ConsolidatedStatementsofOperations" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GrossProfit_81c8f342-47db-4511-a270-dbb314e44c54" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GrossProfit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_7d1dd729-c020-41b6-9aee-552477668419" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_GrossProfit_81c8f342-47db-4511-a270-dbb314e44c54" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_7d1dd729-c020-41b6-9aee-552477668419" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_14f662ab-b9a7-4825-98ad-b561ad311b7f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_GrossProfit_81c8f342-47db-4511-a270-dbb314e44c54" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_14f662ab-b9a7-4825-98ad-b561ad311b7f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_b6954373-b10e-4c42-8e88-6124a52bcfdc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_732ed8ab-1464-4153-b07c-ca5ce298a1f8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_b6954373-b10e-4c42-8e88-6124a52bcfdc" xlink:to="loc_us-gaap_OperatingIncomeLoss_732ed8ab-1464-4153-b07c-ca5ce298a1f8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_6ecd5ce8-f252-4591-becb-d1988cfbdf1b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_b6954373-b10e-4c42-8e88-6124a52bcfdc" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_6ecd5ce8-f252-4591-becb-d1988cfbdf1b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_ec27b581-a467-43f5-8c62-6fa68690ebda" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_4922a697-4585-4bb0-a479-b4da72720a27" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_ec27b581-a467-43f5-8c62-6fa68690ebda" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_4922a697-4585-4bb0-a479-b4da72720a27" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_0c0b0c35-ca06-4d4f-9e80-e76b483aae3b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_ec27b581-a467-43f5-8c62-6fa68690ebda" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_0c0b0c35-ca06-4d4f-9e80-e76b483aae3b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_5f0900f1-06f4-4bda-b44a-3728fe1ace65" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GrossProfit_fecfcdc4-5168-41ac-825d-190202a9330f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GrossProfit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_5f0900f1-06f4-4bda-b44a-3728fe1ace65" xlink:to="loc_us-gaap_GrossProfit_fecfcdc4-5168-41ac-825d-190202a9330f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_923cfa53-72c4-4833-b1df-c090c5fdee22" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingExpenses"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_5f0900f1-06f4-4bda-b44a-3728fe1ace65" xlink:to="loc_us-gaap_OperatingExpenses_923cfa53-72c4-4833-b1df-c090c5fdee22" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_b8a1e75d-bcf3-4a71-8a9f-66f1774b4cc3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_dddf32c8-775e-441e-b60e-674c3775bc7c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_b8a1e75d-bcf3-4a71-8a9f-66f1774b4cc3" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_dddf32c8-775e-441e-b60e-674c3775bc7c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingAndMarketingExpense_a20c1401-6db7-4134-8cba-23656ab530ed" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SellingAndMarketingExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_b8a1e75d-bcf3-4a71-8a9f-66f1774b4cc3" xlink:to="loc_us-gaap_SellingAndMarketingExpense_a20c1401-6db7-4134-8cba-23656ab530ed" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_0be7deba-83dc-4cd2-8754-eaf8670b1e9b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_b8a1e75d-bcf3-4a71-8a9f-66f1774b4cc3" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_0be7deba-83dc-4cd2-8754-eaf8670b1e9b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetImpairmentCharges_30f13656-0295-4d29-adfd-ac655e46b882" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetImpairmentCharges"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_b8a1e75d-bcf3-4a71-8a9f-66f1774b4cc3" xlink:to="loc_us-gaap_AssetImpairmentCharges_30f13656-0295-4d29-adfd-ac655e46b882" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_74e55b54-78dc-4d6e-ab7d-a556cc96e6e0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_b8a1e75d-bcf3-4a71-8a9f-66f1774b4cc3" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_74e55b54-78dc-4d6e-ab7d-a556cc96e6e0" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/ConsolidatedStatementsofComprehensiveIncomeLoss" xlink:type="simple" xlink:href="osur-20230630.xsd#ConsolidatedStatementsofComprehensiveIncomeLoss"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/ConsolidatedStatementsofComprehensiveIncomeLoss" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_5f81385e-51eb-4255-8827-8f07386a0e9c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_c89edecd-5666-4871-802d-f2337ff5043b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_5f81385e-51eb-4255-8827-8f07386a0e9c" xlink:to="loc_us-gaap_NetIncomeLoss_c89edecd-5666-4871-802d-f2337ff5043b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_ce43c461-b3f3-4afc-a822-fb0fef099974" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_5f81385e-51eb-4255-8827-8f07386a0e9c" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_ce43c461-b3f3-4afc-a822-fb0fef099974" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_9baa3070-a69a-4154-8f5b-19ecd9cdb40b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_5f81385e-51eb-4255-8827-8f07386a0e9c" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_9baa3070-a69a-4154-8f5b-19ecd9cdb40b" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/ConsolidatedStatementsofCashFlows" xlink:type="simple" xlink:href="osur-20230630.xsd#ConsolidatedStatementsofCashFlows"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/ConsolidatedStatementsofCashFlows" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_a102a53b-696f-4323-93bd-3dadd42aacf0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_df4b35fb-25bc-497d-b967-3f5a4b8ffa12" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_a102a53b-696f-4323-93bd-3dadd42aacf0" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_df4b35fb-25bc-497d-b967-3f5a4b8ffa12" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_545ae92c-ed54-48f8-94fd-161f486dcee3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_a102a53b-696f-4323-93bd-3dadd42aacf0" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_545ae92c-ed54-48f8-94fd-161f486dcee3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_edd35bdd-ae12-4b05-9cf2-bc4d234503fe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_a102a53b-696f-4323-93bd-3dadd42aacf0" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_edd35bdd-ae12-4b05-9cf2-bc4d234503fe" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_f35dfc79-bed1-4cac-870e-41a338f576bc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_a102a53b-696f-4323-93bd-3dadd42aacf0" xlink:to="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_f35dfc79-bed1-4cac-870e-41a338f576bc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_0193979d-f3a3-4883-9857-22b3daf28468" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_ShareBasedCompensation_0193979d-f3a3-4883-9857-22b3daf28468" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_e8500d27-57d9-4481-909c-9a65db20ca31" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_e8500d27-57d9-4481-909c-9a65db20ca31" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetImpairmentCharges_4255d151-02d6-4dbd-9d12-8c53b17dfddd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetImpairmentCharges"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_AssetImpairmentCharges_4255d151-02d6-4dbd-9d12-8c53b17dfddd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_osur_IncreaseDecreaseInOtherNonCashAmortization_1976ea7e-b117-403d-9d56-4ac1f1f6b417" xlink:href="osur-20230630.xsd#osur_IncreaseDecreaseInOtherNonCashAmortization"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_osur_IncreaseDecreaseInOtherNonCashAmortization_1976ea7e-b117-403d-9d56-4ac1f1f6b417" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProvisionForDoubtfulAccounts_0eb6a63c-a436-4401-9687-5221fee3cdab" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProvisionForDoubtfulAccounts"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_ProvisionForDoubtfulAccounts_0eb6a63c-a436-4401-9687-5221fee3cdab" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForeignCurrencyTransactionGainLossUnrealized_9ee6577c-3759-476b-a39e-114a1e510bc5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ForeignCurrencyTransactionGainLossUnrealized"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_ForeignCurrencyTransactionGainLossUnrealized_9ee6577c-3759-476b-a39e-114a1e510bc5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseInterestExpense_90c41fc5-61cf-4339-8f69-b0497808d7fc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinanceLeaseInterestExpense"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_FinanceLeaseInterestExpense_90c41fc5-61cf-4339-8f69-b0497808d7fc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_de042eea-8149-4e60-ba06-13dc13087e89" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_de042eea-8149-4e60-ba06-13dc13087e89" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnDispositionOfAssets1_b79fd6cf-be83-43ac-9c21-0c448b80ecb3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GainLossOnDispositionOfAssets1"/>
    <link:calculationArc order="9" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_GainLossOnDispositionOfAssets1_b79fd6cf-be83-43ac-9c21-0c448b80ecb3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_42475a90-a8c0-45e2-9257-1392838ae38c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:calculationArc order="10" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_42475a90-a8c0-45e2-9257-1392838ae38c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentForContingentConsiderationLiabilityOperatingActivities_86f763a3-0ae4-4427-b032-18382fde6d73" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentForContingentConsiderationLiabilityOperatingActivities"/>
    <link:calculationArc order="11" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_PaymentForContingentConsiderationLiabilityOperatingActivities_86f763a3-0ae4-4427-b032-18382fde6d73" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_3532c208-9c39-42a2-9d8a-a6ed0425f8ad" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable"/>
    <link:calculationArc order="12" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_3532c208-9c39-42a2-9d8a-a6ed0425f8ad" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInInventories_4eec8b0f-7609-4efc-8b61-097ad5b70757" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInInventories"/>
    <link:calculationArc order="13" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_IncreaseDecreaseInInventories_4eec8b0f-7609-4efc-8b61-097ad5b70757" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_c09c513e-90c9-4fe2-8225-a270172cb4b9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets"/>
    <link:calculationArc order="14" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_c09c513e-90c9-4fe2-8225-a270172cb4b9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayable_f12d728e-c2fa-4821-bd92-f1e04ac03ff3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInAccountsPayable"/>
    <link:calculationArc order="15" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayable_f12d728e-c2fa-4821-bd92-f1e04ac03ff3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_9a8c9a97-deb1-48a5-8776-fcd9bf53c23e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability"/>
    <link:calculationArc order="16" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_9a8c9a97-deb1-48a5-8776-fcd9bf53c23e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccruedLiabilities_fc037485-b958-435d-95e2-1f0f8bc4e9fa" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities"/>
    <link:calculationArc order="17" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_IncreaseDecreaseInAccruedLiabilities_fc037485-b958-435d-95e2-1f0f8bc4e9fa" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_48cb31e5-05e5-4a80-898c-ec34a00ca905" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="18" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_0eead736-7916-4f75-b46f-a0082811a8cc" xlink:to="loc_us-gaap_NetIncomeLoss_48cb31e5-05e5-4a80-898c-ec34a00ca905" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_c09fa5fd-3ede-4939-a563-5bbc1126bb84" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeasePrincipalPayments_ee785bbc-df4b-4f4e-92a3-d7671ac447df" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinanceLeasePrincipalPayments"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_c09fa5fd-3ede-4939-a563-5bbc1126bb84" xlink:to="loc_us-gaap_FinanceLeasePrincipalPayments_ee785bbc-df4b-4f4e-92a3-d7671ac447df" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockOptionsExercised_fcffd6d9-a722-4f87-9b67-48da86ef34b1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_c09fa5fd-3ede-4939-a563-5bbc1126bb84" xlink:to="loc_us-gaap_ProceedsFromStockOptionsExercised_fcffd6d9-a722-4f87-9b67-48da86ef34b1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities_797f1bb5-86e8-4af9-9ad3-05712596d738" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_c09fa5fd-3ede-4939-a563-5bbc1126bb84" xlink:to="loc_us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities_797f1bb5-86e8-4af9-9ad3-05712596d738" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_baab307b-fca7-4e80-b488-b492882296bb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_c09fa5fd-3ede-4939-a563-5bbc1126bb84" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_baab307b-fca7-4e80-b488-b492882296bb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_db5ebd04-ca43-4a5f-9775-9cf726a38380" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_272be5ff-e3d5-457c-b980-f0c37df932be" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_db5ebd04-ca43-4a5f-9775-9cf726a38380" xlink:to="loc_us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_272be5ff-e3d5-457c-b980-f0c37df932be" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_6e5b7888-b141-4257-84c2-47814aad3a68" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_db5ebd04-ca43-4a5f-9775-9cf726a38380" xlink:to="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_6e5b7888-b141-4257-84c2-47814aad3a68" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_osur_PurchaseOfPropertyAndEquipmentUnderGovernmentContracts_b7a4b015-2988-4dfb-8e80-152e800fb30b" xlink:href="osur-20230630.xsd#osur_PurchaseOfPropertyAndEquipmentUnderGovernmentContracts"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_db5ebd04-ca43-4a5f-9775-9cf726a38380" xlink:to="loc_osur_PurchaseOfPropertyAndEquipmentUnderGovernmentContracts_b7a4b015-2988-4dfb-8e80-152e800fb30b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_osur_ProceedsFromFundingUnderGovernmentContract_47f7f55c-b7d0-4852-93cf-76e3b977b7fa" xlink:href="osur-20230630.xsd#osur_ProceedsFromFundingUnderGovernmentContract"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_db5ebd04-ca43-4a5f-9775-9cf726a38380" xlink:to="loc_osur_ProceedsFromFundingUnderGovernmentContract_47f7f55c-b7d0-4852-93cf-76e3b977b7fa" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/SummaryofSignificantAccountingPoliciesSummaryofAvailableforsaleSecuritiesDetail" xlink:type="simple" xlink:href="osur-20230630.xsd#SummaryofSignificantAccountingPoliciesSummaryofAvailableforsaleSecuritiesDetail"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/SummaryofSignificantAccountingPoliciesSummaryofAvailableforsaleSecuritiesDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_a3bf539a-d7a5-40d6-839c-634be8f738f8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_41f775b1-0b64-4129-82d7-6b4ae81c1ef3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_a3bf539a-d7a5-40d6-839c-634be8f738f8" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_41f775b1-0b64-4129-82d7-6b4ae81c1ef3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_c55ab370-8283-48c6-b591-fc942e782bdd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_a3bf539a-d7a5-40d6-839c-634be8f738f8" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_c55ab370-8283-48c6-b591-fc942e782bdd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_6a2382a3-2b66-429d-8c44-283f3c30a9e5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_a3bf539a-d7a5-40d6-839c-634be8f738f8" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_6a2382a3-2b66-429d-8c44-283f3c30a9e5" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/GovernmentCapitalContractsSummaryofGovernmentContractsBalancesIncludedinConsolidatedBalanceSheetDetails" xlink:type="simple" xlink:href="osur-20230630.xsd#GovernmentCapitalContractsSummaryofGovernmentContractsBalancesIncludedinConsolidatedBalanceSheetDetails"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/GovernmentCapitalContractsSummaryofGovernmentContractsBalancesIncludedinConsolidatedBalanceSheetDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsCurrent_b318e99d-e630-4406-b71f-4ba910a66514" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherAssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BilledContractReceivables_f44f5b68-231d-47fc-b4da-89962755d45f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BilledContractReceivables"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OtherAssetsCurrent_b318e99d-e630-4406-b71f-4ba910a66514" xlink:to="loc_us-gaap_BilledContractReceivables_f44f5b68-231d-47fc-b4da-89962755d45f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnbilledContractsReceivable_cc73030e-c51d-4342-b271-f927a2aec804" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_UnbilledContractsReceivable"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OtherAssetsCurrent_b318e99d-e630-4406-b71f-4ba910a66514" xlink:to="loc_us-gaap_UnbilledContractsReceivable_cc73030e-c51d-4342-b271-f927a2aec804" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/GovernmentCapitalContractsSummaryofGovernmentContractsBalancesIncludedinConsolidatedStatementsofCashflowsDetail" xlink:type="simple" xlink:href="osur-20230630.xsd#GovernmentCapitalContractsSummaryofGovernmentContractsBalancesIncludedinConsolidatedStatementsofCashflowsDetail"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/GovernmentCapitalContractsSummaryofGovernmentContractsBalancesIncludedinConsolidatedStatementsofCashflowsDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_49b04821-e319-4e7a-ab06-02fda02870e2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_cabf8f87-8ee0-46ea-8064-e1dcee064d10" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_49b04821-e319-4e7a-ab06-02fda02870e2" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_cabf8f87-8ee0-46ea-8064-e1dcee064d10" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_osur_FundingEarnedNotYetReceived_18a53552-a395-40da-98be-ebddbdeac77d" xlink:href="osur-20230630.xsd#osur_FundingEarnedNotYetReceived"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_49b04821-e319-4e7a-ab06-02fda02870e2" xlink:to="loc_osur_FundingEarnedNotYetReceived_18a53552-a395-40da-98be-ebddbdeac77d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_osur_FundingReceivedAmount_99c039c3-cd0c-4523-9cc1-ffc3934e895c" xlink:href="osur-20230630.xsd#osur_FundingReceivedAmount"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_49b04821-e319-4e7a-ab06-02fda02870e2" xlink:to="loc_osur_FundingReceivedAmount_99c039c3-cd0c-4523-9cc1-ffc3934e895c" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/InventoriesScheduleofInventoriesDetail" xlink:type="simple" xlink:href="osur-20230630.xsd#InventoriesScheduleofInventoriesDetail"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/InventoriesScheduleofInventoriesDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_3dead0cf-0031-4845-8841-002d154c0fec" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InventoryNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryRawMaterialsNetOfReserves_ec19127f-77df-4696-850b-923158d7ab75" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InventoryRawMaterialsNetOfReserves"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_3dead0cf-0031-4845-8841-002d154c0fec" xlink:to="loc_us-gaap_InventoryRawMaterialsNetOfReserves_ec19127f-77df-4696-850b-923158d7ab75" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWorkInProcess_6c8d92c5-cf8d-4606-a53f-200d42c7d2d9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InventoryWorkInProcess"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_3dead0cf-0031-4845-8841-002d154c0fec" xlink:to="loc_us-gaap_InventoryWorkInProcess_6c8d92c5-cf8d-4606-a53f-200d42c7d2d9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryFinishedGoodsNetOfReserves_b5a24b02-994d-436c-b76f-c796703aa94a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InventoryFinishedGoodsNetOfReserves"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_3dead0cf-0031-4845-8841-002d154c0fec" xlink:to="loc_us-gaap_InventoryFinishedGoodsNetOfReserves_b5a24b02-994d-436c-b76f-c796703aa94a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/PropertyPlantandEquipmentNetScheduleofPropertyPlantandEquipmentDetail" xlink:type="simple" xlink:href="osur-20230630.xsd#PropertyPlantandEquipmentNetScheduleofPropertyPlantandEquipmentDetail"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/PropertyPlantandEquipmentNetScheduleofPropertyPlantandEquipmentDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_5ff61e45-8970-40f5-aa78-abffab04a9de" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_76c32d6f-e247-4479-b2e0-677ae4470d0f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_5ff61e45-8970-40f5-aa78-abffab04a9de" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_76c32d6f-e247-4479-b2e0-677ae4470d0f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_785646a3-774e-45ac-a07b-fd99c18f944b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_5ff61e45-8970-40f5-aa78-abffab04a9de" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_785646a3-774e-45ac-a07b-fd99c18f944b" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/AccruedExpensesandOtherCurrentLiabilitiesScheduleofAccruedExpensesandOtherCurrentLiabilitiesDetail" xlink:type="simple" xlink:href="osur-20230630.xsd#AccruedExpensesandOtherCurrentLiabilitiesScheduleofAccruedExpensesandOtherCurrentLiabilitiesDetail"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/AccruedExpensesandOtherCurrentLiabilitiesScheduleofAccruedExpensesandOtherCurrentLiabilitiesDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_osur_AccruedExpensesAndOtherCurrentLiabilities_fb88288e-be4d-4256-9f94-99420548a551" xlink:href="osur-20230630.xsd#osur_AccruedExpensesAndOtherCurrentLiabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_6faec3de-f443-4b11-9f58-8aacf4ececc4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_osur_AccruedExpensesAndOtherCurrentLiabilities_fb88288e-be4d-4256-9f94-99420548a551" xlink:to="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_6faec3de-f443-4b11-9f58-8aacf4ececc4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedProfessionalFeesCurrent_f0b33b83-6c7c-4c95-a838-a95a692392b6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccruedProfessionalFeesCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_osur_AccruedExpensesAndOtherCurrentLiabilities_fb88288e-be4d-4256-9f94-99420548a551" xlink:to="loc_us-gaap_AccruedProfessionalFeesCurrent_f0b33b83-6c7c-4c95-a838-a95a692392b6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesAndExciseTaxPayableCurrent_aa6ed5e7-ea82-474a-b0f8-211ab5c58d33" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SalesAndExciseTaxPayableCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_osur_AccruedExpensesAndOtherCurrentLiabilities_fb88288e-be4d-4256-9f94-99420548a551" xlink:to="loc_us-gaap_SalesAndExciseTaxPayableCurrent_aa6ed5e7-ea82-474a-b0f8-211ab5c58d33" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAccruedLiabilitiesCurrent_5b05de15-f5ec-4ab8-b88e-f1d3a8b7227d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherAccruedLiabilitiesCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_osur_AccruedExpensesAndOtherCurrentLiabilities_fb88288e-be4d-4256-9f94-99420548a551" xlink:to="loc_us-gaap_OtherAccruedLiabilitiesCurrent_5b05de15-f5ec-4ab8-b88e-f1d3a8b7227d" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.orasure.com/role/IncomeTaxesSummaryOfIncomeTaxExpenseDetails" xlink:type="simple" xlink:href="osur-20230630.xsd#IncomeTaxesSummaryOfIncomeTaxExpenseDetails"/>
  <link:calculationLink xlink:role="http://www.orasure.com/role/IncomeTaxesSummaryOfIncomeTaxExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_3de618dc-c7fe-4aea-93bd-3e4f79536383" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StateAndLocalIncomeTaxExpenseBenefitContinuingOperations_e8f02546-565e-4dc3-9757-40992e22a3c7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StateAndLocalIncomeTaxExpenseBenefitContinuingOperations"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_3de618dc-c7fe-4aea-93bd-3e4f79536383" xlink:to="loc_us-gaap_StateAndLocalIncomeTaxExpenseBenefitContinuingOperations_e8f02546-565e-4dc3-9757-40992e22a3c7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForeignIncomeTaxExpenseBenefitContinuingOperations_7f37678d-0f5f-4bf8-861e-3966735f90a3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ForeignIncomeTaxExpenseBenefitContinuingOperations"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_3de618dc-c7fe-4aea-93bd-3e4f79536383" xlink:to="loc_us-gaap_ForeignIncomeTaxExpenseBenefitContinuingOperations_7f37678d-0f5f-4bf8-861e-3966735f90a3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationRepatriationOfForeignEarnings_c96df3c7-2e4f-4c4e-b063-bcbb2ec3f688" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxReconciliationRepatriationOfForeignEarnings"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_3de618dc-c7fe-4aea-93bd-3e4f79536383" xlink:to="loc_us-gaap_IncomeTaxReconciliationRepatriationOfForeignEarnings_c96df3c7-2e4f-4c4e-b063-bcbb2ec3f688" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
