| 13. Round | 28/11/2021 | Southampton FC U23 | - | West Bromwich Albion U23 | 3:1 |  |
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| 15. Round | 17/12/2021 | Norwich City U23 | - | Southampton FC U23 | 4:3 | ||||
| 17. Round | 17/01/2022 | Southampton FC U23 | - | Fulham FC U23 | 2:1 | ||||
| 18. Round | 23/01/2022 | Southampton FC U23 | - | Middlesbrough FC U23 | 1:0 | ||||
| 19. Round | 07/02/2022 | West Bromwich Albion U23 | - | Southampton FC U23 | 0:1 | |
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| 20. Round | 21/02/2022 | Southampton FC U23 | - | Birmingham City U23 | 2:3 | |
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| 21. Round | 26/02/2022 | Southampton FC U23 | - | Nottingham Forest U23 | 4:2 | |
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| 22. Round | 11/03/2022 | Aston Villa U23 | - | Southampton FC U23 | 2:2 |  |
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| 23. Round | 20/03/2022 | Southampton FC U23 | - | Reading FC U23 | 2:1 | |
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| 16. Round | 25/03/2022 | Southampton FC U23 | - | Wolverhampton Wanderers U23 | 2:4 | |
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| 24. Round | 02/04/2022 | Burnley FC U23 | - | Southampton FC U23 | 2:1 | ||||
| 25. Round | 25/04/2022 | Newcastle United U23 | - | Southampton FC U23 | 2:4 | ||||
| 26. Round | 01/05/2022 | Southampton FC U23 | - | Sunderland AFC U23 | 1:0 |
England