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| U | LDU Quito | - | Grêmio Porto Alegre | 0:1 (0:1) | ||
| R | Grêmio Porto Alegre | - | LDU Quito | 1:2 (1:1) | ||
| U: 14.07.2021 00:15 | R: 21.07.2021 00:15 | Winnaars: LDU Quito | ||||
| U | América de Cali | - | Athletico Paranaense | 0:1 (0:0) | ||
| R | Athletico Paranaense | - | América de Cali | 4:1 (1:0) | ||
| U: 14.07.2021 02:30 | R: 21.07.2021 02:30 | Winnaars: Athletico Paranaense | ||||
| U | Sporting Cristal | - | Arsenal de Sarandí | 2:1 (0:0) | ||
| R | Arsenal de Sarandí | - | Sporting Cristal | 1:1 (0:0) | ||
| U: 15.07.2021 00:15 | R: 22.07.2021 00:15 | Winnaars: Sporting Cristal | ||||
| U | Independiente del Valle | - | Red Bull Bragantino | 0:2 (0:1) | ||
| R | Red Bull Bragantino | - | Independiente del Valle | 1:1 (0:1) | ||
| U: 15.07.2021 02:30 | R: 22.07.2021 02:30 | Winnaars: Red Bull Bragantino | ||||
| U | Atlético Junior | - | Libertad | 3:4 (3:2) | ||
| R | Libertad | - | Atlético Junior | 0:1 (0:0) | ||
| U: 15.07.2021 02:30 | R: 22.07.2021 02:30 | Winnaars: Libertad | ||||
| U | Santos FC | - | Independiente | 1:0 (0:0) | ||
| R | Independiente | - | Santos FC | 1:1 (0:1) | ||
| U: 16.07.2021 00:15 | R: 23.07.2021 00:15 | Winnaars: Santos FC | ||||
| U | Nacional | - | Peñarol | 1:2 (0:1) | ||
| R | Peñarol | - | Nacional | 0:1 (0:0) | ||
| U: 16.07.2021 02:30 | R: 23.07.2021 02:30 | Winnaars: Peñarol | ||||
| U | Deportivo Táchira | - | Rosario Central | 2:2 (0:1) | ||
| R | Rosario Central | - | Deportivo Táchira | 1:0 (1:0) | ||
| U: 16.07.2021 02:30 | R: 23.07.2021 02:30 | Winnaars: Rosario Central | ||||
