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| 1st(1st leg) | Patriotas FC | - | Real Santander | 1:0 (0:0) | ||
| 2nd (2nd leg) | Real Santander | - | Patriotas FC | 4:5 (2:1, 3:2, 3:2) pso | ||
| 1st(1st leg): 28/07/2021 21:00 | 2nd (2nd leg): 04/08/2021 21:00 | Winner: Patriotas FC | ||||
| 1st(1st leg) | Atlético Bucaramanga | - | Envigado FC | 1:1 (0:0) | ||
| 2nd (2nd leg) | Envigado FC | - | Atlético Bucaramanga | 1:2 (0:0) | ||
| 1st(1st leg): 29/07/2021 00:00 | 2nd (2nd leg): 05/08/2021 23:30 | Winner: Atlético Bucaramanga | ||||
| 1st(1st leg) | Independiente Medellín | - | Once Caldas | 1:1 (1:1) | ||
| 2nd (2nd leg) | Once Caldas | - | Independiente Medellín | 1:3 (1:1) | ||
| 1st(1st leg): 29/07/2021 02:05 | 2nd (2nd leg): 04/08/2021 23:40 | Winner: Independiente Medellín | ||||
| 1st(1st leg) | Jaguares de Córdoba | - | Barranquilla FC | 3:0 (1:0) | ||
| 2nd (2nd leg) | Barranquilla FC | - | Jaguares de Córdoba | 2:0 (1:0) | ||
| 1st(1st leg): 29/07/2021 23:30 | 2nd (2nd leg): 06/08/2021 02:00 | Winner: Jaguares de Córdoba | ||||
| 1st(1st leg) | Boyacá Chicó | - | Llaneros FC | 1:2 (0:0) | ||
| 2nd (2nd leg) | Llaneros FC | - | Boyacá Chicó | 2:2 (2:1) | ||
| 1st(1st leg): 30/07/2021 01:00 | 2nd (2nd leg): 05/08/2021 21:00 | Winner: Llaneros FC | ||||
| 1st(1st leg) | Deportivo Pereira | - | Boca Juniors de Cali | 1:0 (0:0) | ||
| 2nd (2nd leg) | Boca Juniors de Cali | - | Deportivo Pereira | 0:1 (0:0) | ||
| 1st(1st leg): 30/07/2021 01:40 | 2nd (2nd leg): 05/08/2021 21:00 | Winner: Deportivo Pereira | ||||
| 1st(1st leg) | Alianza Petrolera | - | Millonarios | 1:0 (0:0) | ||
| 2nd (2nd leg) | Millonarios | - | Alianza Petrolera | 1:1 (0:0) | ||
| 1st(1st leg): 05/08/2021 02:05 | 2nd (2nd leg): 19/08/2021 02:00 | Winner: Alianza Petrolera | ||||
