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| H | Rosario Central | - | Red Bull Bragantino | 3:4 (1:3) | ||
| R | Red Bull Bragantino | - | Rosario Central | 1:0 (0:0) | ||
| H: 11.08.2021 00:15 | R: 18.08.2021 00:15 | Sieger: Red Bull Bragantino | ||||
| H | Sporting Cristal | - | Peñarol | 1:3 (0:2) | ||
| R | Peñarol | - | Sporting Cristal | 1:0 (1:0) | ||
| H: 12.08.2021 00:15 | R: 19.08.2021 00:15 | Sieger: Peñarol | ||||
| H | LDU Quito | - | Athletico Paranaense | 1:0 (0:0) | ||
| R | Athletico Paranaense | - | LDU Quito | 4:2 (2:2) | ||
| H: 13.08.2021 00:15 | R: 20.08.2021 00:15 | Sieger: Athletico Paranaense | ||||
| H | Santos FC | - | Libertad | 2:1 (1:0) | ||
| R | Libertad | - | Santos FC | 1:0 (1:0) | ||
| H: 13.08.2021 02:30 | R: 20.08.2021 02:30 | Sieger: Libertad | ||||
