Valledupar FC 3-4 Boca Juniors Cali *
| 22.04.2021 | Boca Juniors Cali | 4-1 | Valledupar FC | |
| 15.04.2021 | Valledupar FC | 2-0 | Boca Juniors Cali | |
Itagüí Leones FC 1-5 Real Santander *
| 21.04.2021 | Real Santander | 2-0 | Itagüí Leones FC | |
| 15.04.2021 | Itagüí Leones FC | 1-3 | Real Santander | |
*Llaneros FC (COL) 1-0 Real Cartagena
| 22.04.2021 | Real Cartagena | 0-1 | Llaneros FC (COL) | |
| 14.04.2021 | Llaneros FC (COL) | 0-0 | Real Cartagena | |
Tigres FC (COL) 1-4 Barranquilla FC *
| 23.04.2021 | Barranquilla FC | 3-0 | Tigres FC (COL) | |
| 16.04.2021 | Tigres FC (COL) | 1-1 | Barranquilla FC | |