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| 1st(1st leg) | Pumas UNAM | - | Cruz Azul | 2:1 (2:0) | ||
| 2nd (2nd leg) | Cruz Azul | - | Pumas UNAM | 0:0 (0:0) | ||
| 1st(1st leg): 06/04/2022 03:00 | 2nd (2nd leg): 13/04/2022 03:00 | Winner: Pumas UNAM | ||||
| 1st(1st leg) | Seattle Sounders | - | New York City FC | 3:1 (2:1) | ||
| 2nd (2nd leg) | New York City FC | - | Seattle Sounders | 1:1 (0:1) | ||
| 1st(1st leg): 07/04/2022 03:00 | 2nd (2nd leg): 14/04/2022 02:00 | Winner: Seattle Sounders | ||||
