| 30. Round | 05/02/2022 | Leyton Orient | - | Colchester United | 0:1 | ||||
| 31. Round | 08/02/2022 | Mansfield Town | - | Colchester United | 2:1 | ||||
| 32. Round | 12/02/2022 | Colchester United | - | Carlisle United | 2:2 |  |
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| 33. Round | 19/02/2022 | Northampton Town | - | Colchester United | 3:0 | ||||
| 22. Round | 22/02/2022 | Colchester United | - | Hartlepool United | 1:2 | ||||
| 34. Round | 26/02/2022 | Colchester United | - | Oldham Athletic | 1:1 | ||||
| 35. Round | 05/03/2022 | Colchester United | - | Port Vale FC | 1:0 | ||||
| 36. Round | 12/03/2022 | Scunthorpe United | - | Colchester United | 1:3 | ||||
| 38. Round | 21/03/2022 | Colchester United | - | Forest Green Rovers | 0:1 | ||||
| 41. Round | 09/04/2022 | Colchester United | - | Stevenage FC | 0:2 | ||||
| 42. Round | 15/04/2022 | Exeter City | - | Colchester United | 2:0 | ||||
| 45. Round | 30/04/2022 | Colchester United | - | Walsall FC | 2:2 |
Ireland