| 1. Journée | 14.08.2021 | Everton FC | - | Southampton FC | 3:1 | ||||
| 2. Journée | 22.08.2021 | Southampton FC | - | Manchester United | 1:1 |  |
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| 3. Journée | 28.08.2021 | Newcastle United | - | Southampton FC | 2:2 | |
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| 4. Journée | 11.09.2021 | Southampton FC | - | West Ham United | 0:0 | ||||
| 6. Journée | 26.09.2021 | Southampton FC | - | Wolverhampton Wanderers | 0:1 | ||||
| 7. Journée | 02.10.2021 | Chelsea FC | - | Southampton FC | 3:1 | |
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| 8. Journée | 16.10.2021 | Southampton FC | - | Leeds United | 1:0 | ||||
| 17. Journée | 15.12.2021 | Crystal Palace | - | Southampton FC | 2:2 | ||||
| 26. Journée | 19.02.2022 | Southampton FC | - | Everton FC | 2:0 | ||||
| 27. Journée | 25.02.2022 | Southampton FC | - | Norwich City | 2:0 | ||||
| 21. Journée | 10.03.2022 | Southampton FC | - | Newcastle United | 1:2 | ||||
| 38. Journée | 22.05.2022 | Leicester City | - | Southampton FC | 4:1 |
Mali