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| 22/12/2021 | 19:00 | Cheltenham Town | - | Blackpool FC | 1:3 (1:2) | |
| 12/01/2022 | 19:00 | Blackburn Rovers | - | Stoke City | 3:0 (2:0) | |
| 19:00 | AFC Bournemouth | - | Queens Park Rangers | 2:0 (1:0) | ||
| 13/01/2022 | 19:00 | Reading FC | - | Manchester United | 1:3 (0:3) | |
| 19:00 | Watford FC | - | Chelsea FC | 2:3 (1:2, 2:2, 2:3) aet | ||
| 14/01/2022 | 19:00 | Leicester City | - | Crewe Alexandra | 1:0 (0:0) | |
| 19:00 | Everton FC | - | Sheffield United | 2:1 (1:0) | ||
| 15/01/2022 | 14:00 | Crystal Palace | - | Wolverhampton Wanderers | 6:7 (1:0, 1:1, 1:1) pso | |
| 17/01/2022 | 19:00 | Newcastle United | - | Colchester United | 3:2 (1:0) | |
| 18/01/2022 | 14:00 | Brighton & Hove Albion | - | Manchester City | 1:0 (0:0) | |
| 19:00 | Liverpool FC | - | Burnley FC | 4:1 (2:0) | ||
| 19:00 | Peterborough United | - | Nottingham Forest | 1:2 (1:1) | ||
| 19:00 | Accrington Stanley | - | Charlton Athletic | 1:2 (1:2) | ||
| 19:00 | Sheffield Wednesday | - | Preston North End | 1:0 (1:0) | ||
| 19/01/2022 | 19:00 | Cambridge United | - | Leeds United | 2:0 (2:0) | |
| 21/01/2022 | 13:00 | Tottenham Hotspur | - | West Bromwich Albion | 6:1 (1:0) |
