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                    <ccc>XXXXXXXX</ccc>
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            <liveTestFlag>LIVE</liveTestFlag>



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            <issuerName>NAUTILUS BIOTECHNOLOGY, INC.</issuerName>
            <secFileNumber>001-39434</secFileNumber>
            <issuerAddress>
                <ns2:street1>2701 Eastlake Avenue East</ns2:street1>
                <ns2:city>Seattle</ns2:city>
                <ns2:stateOrCountry>WA</ns2:stateOrCountry>
                <ns2:zipCode>98102</ns2:zipCode>
            </issuerAddress>
            <issuerContactPhone>(206) 333-2001</issuerContactPhone>
            <nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>MARY GODWIN</nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>
            <relationshipsToIssuer>
                <relationshipToIssuer>Officer</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>8th Floor</ns2:street2>
                    <ns2:city>New York</ns2:city>
                    <ns2:stateOrCountry>NY</ns2:stateOrCountry>
                    <ns2:zipCode>10004</ns2:zipCode>
                </address>
            </brokerOrMarketmakerDetails>
            <noOfUnitsSold>60000</noOfUnitsSold>
            <aggregateMarketValue>131778.00</aggregateMarketValue>
            <noOfUnitsOutstanding>125563965</noOfUnitsOutstanding>
            <approxSaleDate>12/03/2024</approxSaleDate>
            <securitiesExchangeName>NASDAQ</securitiesExchangeName>
        </securitiesInformation>
        <securitiesToBeSold>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <acquiredDate>12/03/2024</acquiredDate>
            <natureOfAcquisitionTransaction>Stock Option Exercise</natureOfAcquisitionTransaction>
            <nameOfPersonfromWhomAcquired>Issuer</nameOfPersonfromWhomAcquired>
            <isGiftTransaction>N</isGiftTransaction>
            <amountOfSecuritiesAcquired>60000</amountOfSecuritiesAcquired>
            <paymentDate>12/03/2024</paymentDate>
            <natureOfPayment>Cash</natureOfPayment>
        </securitiesToBeSold>
        <nothingToReportFlagOnSecuritiesSoldInPast3Months>N</nothingToReportFlagOnSecuritiesSoldInPast3Months>
        <securitiesSoldInPast3Months>
            <sellerDetails>
                <name>MARY GODWIN</name>
                <address>
                    <ns2:street1>2701 Eastlake Avenue East</ns2:street1>
                    <ns2:city>Seattle</ns2:city>
                    <ns2:stateOrCountry>WA</ns2:stateOrCountry>
                    <ns2:zipCode>98102</ns2:zipCode>
                </address>
            </sellerDetails>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <saleDate>11/26/2024</saleDate>
            <amountOfSecuritiesSold>60000</amountOfSecuritiesSold>
            <grossProceeds>136512.00</grossProceeds>
        </securitiesSoldInPast3Months>
        <securitiesSoldInPast3Months>
            <sellerDetails>
                <name>MARY GODWIN</name>
                <address>
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                    <ns2:stateOrCountry>WA</ns2:stateOrCountry>
                    <ns2:zipCode>98102</ns2:zipCode>
                </address>
            </sellerDetails>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <saleDate>11/21/2024</saleDate>
            <amountOfSecuritiesSold>30000</amountOfSecuritiesSold>
            <grossProceeds>70623.00</grossProceeds>
        </securitiesSoldInPast3Months>
        <securitiesSoldInPast3Months>
            <sellerDetails>
                <name>MARY GODWIN</name>
                <address>
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                    <ns2:stateOrCountry>WA</ns2:stateOrCountry>
                    <ns2:zipCode>98102</ns2:zipCode>
                </address>
            </sellerDetails>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <saleDate>11/19/2024</saleDate>
            <amountOfSecuritiesSold>30000</amountOfSecuritiesSold>
            <grossProceeds>68046.00</grossProceeds>
        </securitiesSoldInPast3Months>
        <securitiesSoldInPast3Months>
            <sellerDetails>
                <name>MARY GODWIN</name>
                <address>
                    <ns2:street1>2701 Eastlake Avenue East</ns2:street1>
                    <ns2:city>Seattle</ns2:city>
                    <ns2:stateOrCountry>WA</ns2:stateOrCountry>
                    <ns2:zipCode>98102</ns2:zipCode>
                </address>
            </sellerDetails>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <saleDate>11/11/2024</saleDate>
            <amountOfSecuritiesSold>40000</amountOfSecuritiesSold>
            <grossProceeds>98884.00</grossProceeds>
        </securitiesSoldInPast3Months>
        <securitiesSoldInPast3Months>
            <sellerDetails>
                <name>MARY ELIZABETH GODWIN</name>
                <address>
                    <ns2:street1>2701 Eastlake Avenue East</ns2:street1>
                    <ns2:city>Seattle</ns2:city>
                    <ns2:stateOrCountry>WA</ns2:stateOrCountry>
                    <ns2:zipCode>98102</ns2:zipCode>
                </address>
            </sellerDetails>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <saleDate>11/08/2024</saleDate>
            <amountOfSecuritiesSold>31078</amountOfSecuritiesSold>
            <grossProceeds>78158.06</grossProceeds>
        </securitiesSoldInPast3Months>
        <securitiesSoldInPast3Months>
            <sellerDetails>
                <name>MARY ELIZABETH GODWIN</name>
                <address>
                    <ns2:street1>2701 Eastlake Avenue East</ns2:street1>
                    <ns2:city>Seattle</ns2:city>
                    <ns2:stateOrCountry>WA</ns2:stateOrCountry>
                    <ns2:zipCode>98102</ns2:zipCode>
                </address>
            </sellerDetails>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <saleDate>11/07/2024</saleDate>
            <amountOfSecuritiesSold>28922</amountOfSecuritiesSold>
            <grossProceeds>79642.51</grossProceeds>
        </securitiesSoldInPast3Months>
        <securitiesSoldInPast3Months>
            <sellerDetails>
                <name>MARY ELIZABETH GODWIN</name>
                <address>
                    <ns2:street1>2701 Eastlake Avenue East</ns2:street1>
                    <ns2:city>Seattle</ns2:city>
                    <ns2:stateOrCountry>WA</ns2:stateOrCountry>
                    <ns2:zipCode>98102</ns2:zipCode>
                </address>
            </sellerDetails>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <saleDate>09/23/2024</saleDate>
            <amountOfSecuritiesSold>47031</amountOfSecuritiesSold>
            <grossProceeds>134739.11</grossProceeds>
        </securitiesSoldInPast3Months>
        <securitiesSoldInPast3Months>
            <sellerDetails>
                <name>MARY ELIZABETH GODWIN</name>
                <address>
                    <ns2:street1>2701 Eastlake Avenue East</ns2:street1>
                    <ns2:city>Seattle</ns2:city>
                    <ns2:stateOrCountry>WA</ns2:stateOrCountry>
                    <ns2:zipCode>98102</ns2:zipCode>
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            </sellerDetails>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <saleDate>09/17/2024</saleDate>
            <amountOfSecuritiesSold>35000</amountOfSecuritiesSold>
            <grossProceeds>99865.50</grossProceeds>
        </securitiesSoldInPast3Months>
        <noticeSignature>
            <noticeDate>12/03/2024</noticeDate>
            <planAdoptionDates/>
            <signature>/s/ Mary Elizabeth Godwin</signature>
        </noticeSignature>
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144
0001439716
XXXXXXXX
LIVE
0001808805
NAUTILUS BIOTECHNOLOGY, INC.
001-39434
2701 Eastlake Avenue East
Seattle
WA
98102
(206) 333-2001
MARY GODWIN
Officer
Common
Morgan Stanley Smith Barney LLC Executive Financial Services
1 New York Plaza
8th Floor
New York
NY
10004
60000
131778.00
125563965
12/03/2024
NASDAQ
Common
12/03/2024
Stock Option Exercise
Issuer
N
60000
12/03/2024
Cash
N
MARY GODWIN
2701 Eastlake Avenue East
Seattle
WA
98102
Common
11/26/2024
60000
136512.00
MARY GODWIN
2701 Eastlake Avenue East
Seattle
WA
98102
Common
11/21/2024
30000
70623.00
MARY GODWIN
2701 Eastlake Avenue East
Seattle
WA
98102
Common
11/19/2024
30000
68046.00
MARY GODWIN
2701 Eastlake Avenue East
Seattle
WA
98102
Common
11/11/2024
40000
98884.00
MARY ELIZABETH GODWIN
2701 Eastlake Avenue East
Seattle
WA
98102
Common
11/08/2024
31078
78158.06
MARY ELIZABETH GODWIN
2701 Eastlake Avenue East
Seattle
WA
98102
Common
11/07/2024
28922
79642.51
MARY ELIZABETH GODWIN
2701 Eastlake Avenue East
Seattle
WA
98102
Common
09/23/2024
47031
134739.11
MARY ELIZABETH GODWIN
2701 Eastlake Avenue East
Seattle
WA
98102
Common
09/17/2024
35000
99865.50
12/03/2024
/s/ Mary Elizabeth Godwin