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| 1st(1st leg) | América de Cali | - | Deportivo Cali | 2:2 (1:1) | ||
| 2nd (2nd leg) | Deportivo Cali | - | América de Cali | 1:0 (1:0) | ||
| 1st(1st leg): 09/09/2021 00:00 | 2nd (2nd leg): 16/09/2021 02:00 | Winner: Deportivo Cali | ||||
| 1st(1st leg) | Santa Fe | - | Atlético Nacional | 2:1 (1:1) | ||
| 2nd (2nd leg) | Atlético Nacional | - | Santa Fe | 3:1 (1:0, 1:0, 1:0) pso | ||
| 1st(1st leg): 09/09/2021 02:05 | 2nd (2nd leg): 15/09/2021 23:30 | Winner: Atlético Nacional | ||||
| 1st(1st leg) | La Equidad | - | Deportes Tolima | 0:0 (0:0) | ||
| 2nd (2nd leg) | Deportes Tolima | - | La Equidad | 2:0 (0:0) | ||
| 1st(1st leg): 09/09/2021 20:00 | 2nd (2nd leg): 16/09/2021 23:30 | Winner: Deportes Tolima | ||||
| 1st(1st leg) | Deportivo Pasto | - | Deportivo Pereira | 3:2 (1:1) | ||
| 2nd (2nd leg) | Deportivo Pereira | - | Deportivo Pasto | 2:1 (1:0, 2:1, 2:1) pso | ||
| 1st(1st leg): 10/09/2021 02:30 | 2nd (2nd leg): 17/09/2021 02:00 | Winner: Deportivo Pereira | ||||
