<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2020-09-23</periodOfReport>

    <noSecuritiesOwned>1</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001053691</issuerCik>
        <issuerName>Diffusion Pharmaceuticals Inc.</issuerName>
        <issuerTradingSymbol>DFFN</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001828068</rptOwnerCik>
            <rptOwnerName>ELDER WILLIAM ROBERT</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>1317 CARLTON AVENUE, SUITE 200</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>CHARLOTTESVILLE</rptOwnerCity>
            <rptOwnerState>VA</rptOwnerState>
            <rptOwnerZipCode>22902</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isOfficer>1</isOfficer>
            <officerTitle>GC &amp; Secretary</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <ownerSignature>
        <signatureName>/s/ William R. Elder</signatureName>
        <signatureDate>2020-10-14</signatureDate>
    </ownerSignature>
</ownershipDocument>
