| 5. Round | 19/09/2021 | Southampton FC U23 | - | Burnley FC U23 | 0:2 | ||||
| 6. Round | 27/09/2021 | Birmingham City U23 | - | Southampton FC U23 | 3:2 |  |
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| 7. Round | 01/10/2021 | Southampton FC U23 | - | Stoke City U23 | 1:1 | ||||
| 9. Round | 25/10/2021 | Reading FC U23 | - | Southampton FC U23 | 0:1 | |
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| 12. Round | 21/11/2021 | Sunderland AFC U23 | - | Southampton FC U23 | 3:2 | |
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| 15. Round | 17/12/2021 | Norwich City U23 | - | Southampton FC U23 | 4:3 | |
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| 17. Round | 17/01/2022 | Southampton FC U23 | - | Fulham FC U23 | 2:1 | |
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| 18. Round | 23/01/2022 | Southampton FC U23 | - | Middlesbrough FC U23 | 1:0 |
England