| 1. Jornada | 23.01.2022 | Valledupar FC | - | Real Santander | 1:0 |  |
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| 2. Jornada | 30.01.2022 | Real Santander | - | Tigres FC | 0:0 | ||||
| 3. Jornada | 06.02.2022 | Fortaleza FC | - | Real Santander | 2:3 | |
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| 4. Jornada | 13.02.2022 | Real Santander | - | Barranquilla FC | 2:3 | ||||
| 5. Jornada | 20.02.2022 | Atlético Huila | - | Real Santander | 1:1 | |
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| 6. Jornada | 27.02.2022 | Real Santander | - | Real Cartagena | 1:2 | ||||
| 8. Jornada | 10.03.2022 | Atlético FC | - | Real Santander | 0:1 | |
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| 10. Jornada | 26.03.2022 | Bogotá FC | - | Real Santander | 2:1 | ||||
| 11. Jornada | 03.04.2022 | Real Santander | - | Orsomarso SC | 0:0 |
Colombia