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| 1st(1st leg) | Montevideo City Torque | - | Barcelona | 1:1 (0:1) | ||
| 2nd (2nd leg) | Barcelona | - | Montevideo City Torque | 8:7 (0:0, 0:0) pso | ||
| 1st(1st leg): 09/02/2022 00:30 | 2nd (2nd leg): 16/02/2022 00:30 | Winner: Barcelona | ||||
| 1st(1st leg) | Deportivo Lara | - | Bolívar | 2:3 (2:3) | ||
| 2nd (2nd leg) | Bolívar | - | Deportivo Lara | 4:0 (1:0) | ||
| 1st(1st leg): 09/02/2022 22:15 | 2nd (2nd leg): 16/02/2022 22:15 | Winner: Bolívar | ||||
| 1st(1st leg) | Universidad Cesar Vallejo | - | Club Olimpia | 0:1 (0:1) | ||
| 2nd (2nd leg) | Club Olimpia | - | Universidad Cesar Vallejo | 2:0 (1:0) | ||
| 1st(1st leg): 10/02/2022 00:30 | 2nd (2nd leg): 17/02/2022 00:30 | Winner: Club Olimpia | ||||
