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| 1st(1st leg) | Nacional | - | Unión de Santa Fe | 2:0 (2:0) | ||
| 2nd (2nd leg) | Unión de Santa Fe | - | Nacional | 1:2 (0:0) | ||
| 1st(1st leg): 28/06/2022 23:15 | 2nd (2nd leg): 05/07/2022 23:15 | Winner: Nacional | ||||
| 1st(1st leg) | Colo-Colo | - | Internacional | 2:0 (1:0) | ||
| 2nd (2nd leg) | Internacional | - | Colo-Colo | 4:1 (2:1) | ||
| 1st(1st leg): 29/06/2022 01:30 | 2nd (2nd leg): 06/07/2022 01:30 | Winner: Internacional | ||||
| 1st(1st leg) | The Strongest | - | Ceará - CE | 1:2 (1:0) | ||
| 2nd (2nd leg) | Ceará - CE | - | The Strongest | 3:0 (2:0) | ||
| 1st(1st leg): 29/06/2022 23:15 | 2nd (2nd leg): 06/07/2022 23:15 | Winner: Ceará - CE | ||||
| 1st(1st leg) | Deportivo Táchira | - | Santos FC | 1:1 (1:0) | ||
| 2nd (2nd leg) | Santos FC | - | Deportivo Táchira | 2:4 (0:1, 1:1) pso | ||
| 1st(1st leg): 30/06/2022 01:30 | 2nd (2nd leg): 07/07/2022 01:30 | Winner: Deportivo Táchira | ||||
| 1st(1st leg) | Deportivo Cali | - | FBC Melgar | 0:0 (0:0) | ||
| 2nd (2nd leg) | FBC Melgar | - | Deportivo Cali | 2:1 (0:0) | ||
| 1st(1st leg): 30/06/2022 01:30 | 2nd (2nd leg): 07/07/2022 01:30 | Winner: FBC Melgar | ||||
| 1st(1st leg) | Independiente del Valle | - | Lanús | 2:1 (1:0) | ||
| 2nd (2nd leg) | Lanús | - | Independiente del Valle | 0:0 (0:0) | ||
| 1st(1st leg): 30/06/2022 23:15 | 2nd (2nd leg): 07/07/2022 23:15 | Winner: Independiente del Valle | ||||
| 1st(1st leg) | Universidad Católica | - | São Paulo FC | 2:4 (0:3) | ||
| 2nd (2nd leg) | São Paulo FC | - | Universidad Católica | 4:1 (2:0) | ||
| 1st(1st leg): 01/07/2022 01:30 | 2nd (2nd leg): 08/07/2022 01:30 | Winner: São Paulo FC | ||||
| 1st(1st leg) | Club Olimpia | - | Atlético Goianiense | 2:0 (1:0) | ||
| 2nd (2nd leg) | Atlético Goianiense | - | Club Olimpia | 5:3 (2:0, 2:0) pso | ||
| 1st(1st leg): 01/07/2022 01:30 | 2nd (2nd leg): 08/07/2022 01:30 | Winner: Atlético Goianiense | ||||
