| 1. Round | 15/08/2021 | Southampton FC U23 | - | Norwich City U23 | 0:3 |  |
|||
| 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 |  |
|
||
| 8. Round | 18/10/2021 | Wolverhampton Wanderers U23 | - | Southampton FC U23 | 0:1 | ||||
| 9. Round | 25/10/2021 | Reading FC U23 | - | Southampton FC U23 | 0:1 | |
|||
| 10. Round | 31/10/2021 | Southampton FC U23 | - | Aston Villa U23 | 4:0 | |
|||
| 12. Round | 21/11/2021 | Sunderland AFC U23 | - | Southampton FC U23 | 3:2 | |
|||
| 13. Round | 28/11/2021 | Southampton FC U23 | - | West Bromwich Albion U23 | 3:1 | ||||
| 14. Round | 06/12/2021 | Stoke City U23 | - | Southampton FC U23 | 3:0 |
England