| 1. Round | 21/01/2022 | Santa Fe | - | La Equidad | 1:1 |  |
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| 2. Round | 25/01/2022 | Santa Fe | - | Águilas Doradas | 3:0 | |
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| 3. Round | 29/01/2022 | Cortuluá | - | Santa Fe | 1:1 |  |
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| 4. Round | 03/02/2022 | Santa Fe | - | Atlético Junior | 2:1 | ||||
| 5. Round | 08/02/2022 | América de Cali | - | Santa Fe | 2:2 | |
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| 8. Round | 19/02/2022 | Santa Fe | - | Independiente Medellín | 1:0 | ||||
| 9. Round | 01/03/2022 | Patriotas FC | - | Santa Fe | 1:1 | ||||
| 10. Round | 06/03/2022 | Santa Fe | - | Millonarios | 0:3 | ||||
| 15. Round | 10/04/2022 | Envigado FC | - | Santa Fe | 1:0 | ||||
| 16. Round | 16/04/2022 | Santa Fe | - | Alianza Petrolera | 0:1 |
Colombia