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| 1st(1st leg) | América - MG | - | Barcelona | 0:0 (0:0) | ||
| 2nd (2nd leg) | Barcelona | - | América - MG | 4:5 (0:0, 0:0) pso | ||
| 1st(1st leg): 09/03/2022 00:30 | 2nd (2nd leg): 16/03/2022 00:30 | Winner: América - MG | ||||
| 1st(1st leg) | Everton | - | Estudiantes | 0:1 (0:0) | ||
| 2nd (2nd leg) | Estudiantes | - | Everton | 1:0 (1:0) | ||
| 1st(1st leg): 09/03/2022 22:15 | 2nd (2nd leg): 16/03/2022 22:15 | Winner: Estudiantes | ||||
| 1st(1st leg) | Fluminense RJ | - | Club Olimpia | 3:1 (1:1) | ||
| 2nd (2nd leg) | Club Olimpia | - | Fluminense RJ | 2:0 (1:0) pso | ||
| 1st(1st leg): 10/03/2022 00:30 | 2nd (2nd leg): 17/03/2022 00:30 | Winner: Club Olimpia | ||||
| 1st(1st leg) | Universidad Catolica | - | The Strongest | 0:0 (0:0) | ||
| 2nd (2nd leg) | The Strongest | - | Universidad Catolica | 2:1 (1:1) | ||
| 1st(1st leg): 11/03/2022 00:30 | 2nd (2nd leg): 18/03/2022 00:30 | Winner: The Strongest | ||||
