| 1. Round | 23/08/2021 | Sampdoria | - | AC Milan | 0:1 |  |
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| 8. Round | 17/10/2021 | Cagliari Calcio | - | Sampdoria | 3:1 | ||||
| 9. Round | 22/10/2021 | Sampdoria | - | Spezia Calcio | 2:1 | ||||
| 10. Round | 27/10/2021 | Sampdoria | - | Atalanta | 1:3 | ||||
| 11. Round | 30/10/2021 | Torino FC | - | Sampdoria | 3:0 | ||||
| 12. Round | 07/11/2021 | Sampdoria | - | Bologna FC | 1:2 | |
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| 13. Round | 21/11/2021 | US Salernitana 1919 | - | Sampdoria | 0:2 | ||||
| 14. Round | 27/11/2021 | Sampdoria | - | Hellas Verona | 3:1 | ||||
| 15. Round | 30/11/2021 | ACF Fiorentina | - | Sampdoria | 3:1 |  |
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| 16. Round | 05/12/2021 | Sampdoria | - | Lazio Roma | 1:3 | |
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| 17. Round | 10/12/2021 | Genoa CFC | - | Sampdoria | 1:3 | |
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| 18. Round | 19/12/2021 | Sampdoria | - | Venezia FC | 1:1 | |
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| 19. Round | 22/12/2021 | AS Roma | - | Sampdoria | 1:1 | |
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| 20. Round | 06/01/2022 | Sampdoria | - | Cagliari Calcio | 1:2 | |
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| 21. Round | 09/01/2022 | SSC Napoli | - | Sampdoria | 1:0 | ||||
| 22. Round | 15/01/2022 | Sampdoria | - | Torino FC | 1:2 | ||||
| 23. Round | 23/01/2022 | Spezia Calcio | - | Sampdoria | 1:0 | ||||
| 24. Round | 06/02/2022 | Sampdoria | - | Sassuolo Calcio | 4:0 |
Italy
