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| 1st(1st leg) | Atlético FC | - | Llaneros FC | 0:0 (0:0) | ||
| 2nd (2nd leg) | Llaneros FC | - | Atlético FC | 4:0 (3:0) | ||
| 1st(1st leg): 10/03/2021 20:00 | 2nd (2nd leg): 18/03/2021 20:00 | Winner: Llaneros FC | ||||
| 1st(1st leg) | Orsomarso SC | - | Valledupar FC | 0:0 (0:0) | ||
| 2nd (2nd leg) | Valledupar FC | - | Orsomarso SC | 1:0 (0:0) | ||
| 1st(1st leg): 10/03/2021 21:00 | 2nd (2nd leg): 17/03/2021 20:00 | Winner: Valledupar FC | ||||
| 1st(1st leg) | Tigres FC | - | Bogotá FC | 0:1 (0:0) | ||
| 2nd (2nd leg) | Bogotá FC | - | Tigres FC | 0:2 (0:0) | ||
| 1st(1st leg): 10/03/2021 23:00 | 2nd (2nd leg): 19/03/2021 00:40 | Winner: Tigres FC | ||||
| 1st(1st leg) | Barranquilla FC | - | Deportes Quindío | 1:1 (1:0) | ||
| 2nd (2nd leg) | Deportes Quindío | - | Barranquilla FC | 0:1 (0:0) | ||
| 1st(1st leg): 11/03/2021 01:05 | 2nd (2nd leg): 17/03/2021 22:30 | Winner: Barranquilla FC | ||||
| 1st(1st leg) | Fortaleza FC | - | Leones FC | 0:0 (0:0) | ||
| 2nd (2nd leg) | Leones FC | - | Fortaleza FC | 2:1 (2:1) | ||
| 1st(1st leg): 11/03/2021 20:00 | 2nd (2nd leg): 17/03/2021 20:00 | Winner: Leones FC | ||||
| 1st(1st leg) | Real Santander | - | Cortuluá | 1:1 (0:1) | ||
| 2nd (2nd leg) | Cortuluá | - | Real Santander | 1:2 (1:1) | ||
| 1st(1st leg): 11/03/2021 20:15 | 2nd (2nd leg): 18/03/2021 20:10 | Winner: Real Santander | ||||
| 1st(1st leg) | Real Cartagena | - | Atlético Huila | 2:1 (0:1) | ||
| 2nd (2nd leg) | Atlético Huila | - | Real Cartagena | 2:3 (1:0) | ||
| 1st(1st leg): 11/03/2021 22:30 | 2nd (2nd leg): 18/03/2021 01:00 | Winner: Real Cartagena | ||||
| 1st(1st leg) | Boca Juniors de Cali | - | Unión Magdalena | 1:0 (1:0) | ||
| 2nd (2nd leg) | Unión Magdalena | - | Boca Juniors de Cali | 1:1 (1:0) | ||
| 1st(1st leg): 18/03/2021 20:00 | 2nd (2nd leg): 25/03/2021 21:00 | Winner: Boca Juniors de Cali | ||||
