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| H | Red Bull Bragantino | - | Libertad | 2:0 (1:0) | ||
| R | Libertad | - | Red Bull Bragantino | 1:3 (0:1) | ||
| H: 23.09.2021 00:15 | R: 30.09.2021 00:15 | Sieger: Red Bull Bragantino | ||||
| H | Peñarol | - | Athletico Paranaense | 1:2 (1:1) | ||
| R | Athletico Paranaense | - | Peñarol | 2:0 (1:0) | ||
| H: 24.09.2021 02:30 | R: 01.10.2021 02:30 | Sieger: Athletico Paranaense | ||||
