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            <liveTestFlag>LIVE</liveTestFlag>



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            <issuerCik>0001701108</issuerCik>
            <issuerName>SPERO THERAPEUTICS, INC.</issuerName>
            <secFileNumber>001-38266</secFileNumber>
            <issuerAddress>
                <ns2:street1>675 Massachusetts Avenue, 14th  Floor</ns2:street1>
                <ns2:city>Cambridge</ns2:city>
                <ns2:stateOrCountry>MA</ns2:stateOrCountry>
                <ns2:zipCode>02139</ns2:zipCode>
            </issuerAddress>
            <issuerContactPhone>(857) 242-1600</issuerContactPhone>
            <nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>SATYAVRAT SHUKLA</nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>
            <relationshipsToIssuer>
                <relationshipToIssuer>Officer</relationshipToIssuer>
                <relationshipToIssuer>Director</relationshipToIssuer>
            </relationshipsToIssuer>
        </issuerInfo>
        <securitiesInformation>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <brokerOrMarketmakerDetails>
                <name>Morgan Stanley Smith Barney LLC Executive Financial Services</name>
                <address>
                    <ns2:street1>1 New York Plaza</ns2:street1>
                    <ns2:street2>38th Floor</ns2:street2>
                    <ns2:city>New York</ns2:city>
                    <ns2:stateOrCountry>NY</ns2:stateOrCountry>
                    <ns2:zipCode>10004</ns2:zipCode>
                </address>
            </brokerOrMarketmakerDetails>
            <noOfUnitsSold>45093</noOfUnitsSold>
            <aggregateMarketValue>65466.02</aggregateMarketValue>
            <noOfUnitsOutstanding>52999317</noOfUnitsOutstanding>
            <approxSaleDate>02/05/2024</approxSaleDate>
            <securitiesExchangeName>NASDAQ</securitiesExchangeName>
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        <securitiesToBeSold>
            <securitiesClassTitle>COMMON</securitiesClassTitle>
            <acquiredDate>02/01/2024</acquiredDate>
            <natureOfAcquisitionTransaction>Restricted Stock</natureOfAcquisitionTransaction>
            <nameOfPersonfromWhomAcquired>ISSUER</nameOfPersonfromWhomAcquired>
            <isGiftTransaction>N</isGiftTransaction>
            <amountOfSecuritiesAcquired>45093</amountOfSecuritiesAcquired>
            <paymentDate>02/01/2024</paymentDate>
            <natureOfPayment>Not Applicable</natureOfPayment>
        </securitiesToBeSold>
        <nothingToReportFlagOnSecuritiesSoldInPast3Months>N</nothingToReportFlagOnSecuritiesSoldInPast3Months>
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                <address>
                    <ns2:street1>675 Massachusetts Avenue, 14th  Floor</ns2:street1>
                    <ns2:city>Cambridge</ns2:city>
                    <ns2:stateOrCountry>MA</ns2:stateOrCountry>
                    <ns2:zipCode>02139</ns2:zipCode>
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            <securitiesClassTitle>Common</securitiesClassTitle>
            <saleDate>02/02/2024</saleDate>
            <amountOfSecuritiesSold>30901</amountOfSecuritiesSold>
            <grossProceeds>42192.00</grossProceeds>
        </securitiesSoldInPast3Months>
        <noticeSignature>
            <noticeDate>02/05/2024</noticeDate>
            <planAdoptionDates>
                <planAdoptionDate>05/24/2023</planAdoptionDate>
            </planAdoptionDates>
            <signature>/s/ Satyavrat Shukla</signature>
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144
0001782817
XXXXXXXX
LIVE
0001701108
SPERO THERAPEUTICS, INC.
001-38266
675 Massachusetts Avenue, 14th  Floor
Cambridge
MA
02139
(857) 242-1600
SATYAVRAT SHUKLA
Officer
Director
Common
Morgan Stanley Smith Barney LLC Executive Financial Services
1 New York Plaza
38th Floor
New York
NY
10004
45093
65466.02
52999317
02/05/2024
NASDAQ
COMMON
02/01/2024
Restricted Stock
ISSUER
N
45093
02/01/2024
Not Applicable
N
SATYAVRAT SHUKLA
675 Massachusetts Avenue, 14th  Floor
Cambridge
MA
02139
Common
02/02/2024
30901
42192.00
02/05/2024
05/24/2023
/s/ Satyavrat Shukla