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| U | Montevideo Wanderers | - | Bolívar | 1:0 (0:0) | ||
| R | Bolívar | - | Montevideo Wanderers | 5:0 (2:0) | ||
| U: 09.03.2021 23:15 | R: 16.03.2021 23:15 | Winnaars: Bolívar | ||||
| U | Santos FC | - | Deportivo Lara | 2:1 (0:0) | ||
| R | Deportivo Lara | - | Santos FC | 1:1 (0:1) | ||
| U: 09.03.2021 23:15 | R: 16.03.2021 23:15 | Winnaars: Santos FC | ||||
| U | Unión Española | - | Independiente del Valle | 1:0 (0:0) | ||
| R | Independiente del Valle | - | Unión Española | 6:2 (4:0) | ||
| U: 10.03.2021 01:30 | R: 17.03.2021 01:30 | Winnaars: Independiente del Valle | ||||
| U | Universidad Catolica | - | Libertad | 0:1 (0:1) | ||
| R | Libertad | - | Universidad Catolica | 2:2 (1:0) | ||
| U: 10.03.2021 23:15 | R: 17.03.2021 23:15 | Winnaars: Libertad | ||||
| U | Grêmio Porto Alegre | - | Ayacucho FC | 6:1 (4:0) | ||
| R | Ayacucho FC | - | Grêmio Porto Alegre | 1:2 (1:1) | ||
| U: 11.03.2021 01:30 | R: 17.03.2021 01:30 | Winnaars: Grêmio Porto Alegre | ||||
| U | Universidad de Chile | - | San Lorenzo | 1:1 (0:0) | ||
| R | San Lorenzo | - | Universidad de Chile | 2:0 (1:0) | ||
| U: 11.03.2021 01:30 | R: 18.03.2021 01:30 | Winnaars: San Lorenzo | ||||
| U | Caracas FC | - | Atlético Junior | 1:2 (1:0) | ||
| R | Atlético Junior | - | Caracas FC | 3:1 (1:0) | ||
| U: 11.03.2021 01:30 | R: 18.03.2021 01:30 | Winnaars: Atlético Junior | ||||
| U | Guaraní | - | Atlético Nacional | 0:2 (0:1) | ||
| R | Atlético Nacional | - | Guaraní | 3:0 (2:0) | ||
| U: 12.03.2021 01:30 | R: 19.03.2021 01:30 | Winnaars: Atlético Nacional | ||||
