| 1. Jornada | 23.01.2022 | Valledupar FC | - | Real Santander | 1:0 | ||||
| 2. Jornada | 30.01.2022 | Real Santander | - | Tigres FC | 0:0 | ||||
| 3. Jornada | 06.02.2022 | Fortaleza FC | - | Real Santander | 2:3 | ||||
| 4. Jornada | 13.02.2022 | Real Santander | - | Barranquilla FC | 2:3 |  |
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| 5. Jornada | 20.02.2022 | Atlético Huila | - | Real Santander | 1:1 | ||||
| 6. Jornada | 27.02.2022 | Real Santander | - | Real Cartagena | 1:2 | ||||
| 8. Jornada | 10.03.2022 | Atlético FC | - | Real Santander | 0:1 | ||||
| 9. Jornada | 21.03.2022 | Real Santander | - | Leones FC | 0:4 | ||||
| 11. Jornada | 03.04.2022 | Real Santander | - | Orsomarso SC | 0:0 | ||||
| 12. Jornada | 10.04.2022 | Llaneros FC | - | Real Santander | 2:2 | ||||
| 13. Jornada | 16.04.2022 | Real Santander | - | Deportes Quindío | 0:1 | ||||
| 14. Jornada | 26.04.2022 | Boyacá Chicó | - | Real Santander | 2:1 | ||||
| 15. Jornada | 03.05.2022 | Real Santander | - | Boca Juniors de Cali | 1:1 |
Colombia