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| 1st(1st leg) | La Equidad | - | Llaneros FC | 1:0 (0:0) | ||
| 2nd (2nd leg) | Llaneros FC | - | La Equidad | 0:0 (0:0) | ||
| 1st(1st leg): 25/08/2021 20:00 | 2nd (2nd leg): 01/09/2021 21:00 | Winner: La Equidad | ||||
| 1st(1st leg) | Atlético Junior | - | Deportivo Pereira | 4:3 (1:0) | ||
| 2nd (2nd leg) | Deportivo Pereira | - | Atlético Junior | 2:0 (1:0) | ||
| 1st(1st leg): 26/08/2021 00:00 | 2nd (2nd leg): 02/09/2021 02:00 | Winner: Deportivo Pereira | ||||
| 1st(1st leg) | Deportes Tolima | - | Águilas Doradas | 1:0 (0:0) | ||
| 2nd (2nd leg) | Águilas Doradas | - | Deportes Tolima | 0:0 (0:0) | ||
| 1st(1st leg): 26/08/2021 01:00 | 2nd (2nd leg): 03/09/2021 00:00 | Winner: Deportes Tolima | ||||
| 1st(1st leg) | Deportivo Pasto | - | Alianza Petrolera | 3:1 (2:0) | ||
| 2nd (2nd leg) | Alianza Petrolera | - | Deportivo Pasto | 2:3 (1:2) | ||
| 1st(1st leg): 26/08/2021 02:00 | 2nd (2nd leg): 03/09/2021 01:00 | Winner: Deportivo Pasto | ||||
| 1st(1st leg) | Deportivo Cali | - | Independiente Medellín | 2:2 (1:1) | ||
| 2nd (2nd leg) | Independiente Medellín | - | Deportivo Cali | 1:3 (1:0) | ||
| 1st(1st leg): 26/08/2021 02:05 | 2nd (2nd leg): 03/09/2021 02:10 | Winner: Deportivo Cali | ||||
| 1st(1st leg) | Santa Fe | - | Atlético Bucaramanga | 1:0 (1:0) | ||
| 2nd (2nd leg) | Atlético Bucaramanga | - | Santa Fe | 0:1 (0:0) | ||
| 1st(1st leg): 26/08/2021 20:00 | 2nd (2nd leg): 03/09/2021 00:00 | Winner: Santa Fe | ||||
| 1st(1st leg) | América de Cali | - | Jaguares de Córdoba | 0:0 (0:0) | ||
| 2nd (2nd leg) | Jaguares de Córdoba | - | América de Cali | 5:6 (0:1, 1:1, 1:1) pso | ||
| 1st(1st leg): 27/08/2021 00:00 | 2nd (2nd leg): 01/09/2021 23:30 | Winner: América de Cali | ||||
| 1st(1st leg) | Atlético Nacional | - | Patriotas FC | 3:0 (2:0) | ||
| 2nd (2nd leg) | Patriotas FC | - | Atlético Nacional | 1:2 (0:1) | ||
| 1st(1st leg): 27/08/2021 02:05 | 2nd (2nd leg): 03/09/2021 00:00 | Winner: Atlético Nacional | ||||
