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| 1st(1st leg) | Llaneros FC | - | Real Cartagena | 0:0 (0:0) | ||
| 2nd (2nd leg) | Real Cartagena | - | Llaneros FC | 0:1 (0:0) | ||
| 1st(1st leg): 14/04/2021 21:30 | 2nd (2nd leg): 22/04/2021 01:40 | Winner: Llaneros FC | ||||
| 1st(1st leg) | Valledupar FC | - | Boca Juniors de Cali | 2:0 (0:0) | ||
| 2nd (2nd leg) | Boca Juniors de Cali | - | Valledupar FC | 4:1 (3:1) | ||
| 1st(1st leg): 14/04/2021 23:30 | 2nd (2nd leg): 22/04/2021 21:15 | Winner: Boca Juniors de Cali | ||||
| 1st(1st leg) | Leones FC | - | Real Santander | 1:3 (1:3) | ||
| 2nd (2nd leg) | Real Santander | - | Leones FC | 2:0 (1:0) | ||
| 1st(1st leg): 15/04/2021 01:40 | 2nd (2nd leg): 21/04/2021 21:15 | Winner: Real Santander | ||||
| 1st(1st leg) | Tigres FC | - | Barranquilla FC | 1:1 (0:0) | ||
| 2nd (2nd leg) | Barranquilla FC | - | Tigres FC | 3:0 (1:0) | ||
| 1st(1st leg): 15/04/2021 23:30 | 2nd (2nd leg): 23/04/2021 01:40 | Winner: Barranquilla FC | ||||
