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| H (Match allé) | Pumas UNAM | - | Atlas Guadalajara | 3:2 (2:2) | ||
| R (match retour) | Atlas Guadalajara | - | Pumas UNAM | 4:0 (0:0) | ||
| H (Match allé): 11.05.2022 17:00 | R (match retour): 14.05.2022 16:00 | vainqueur: Atlas Guadalajara | ||||
| H (Match allé) | Club Tijuana | - | Santos Laguna | 1:1 (0:0) | ||
| R (match retour) | Santos Laguna | - | Club Tijuana | 4:1 (1:1) | ||
| H (Match allé): 12.05.2022 21:45 | R (match retour): 15.05.2022 17:00 | vainqueur: Santos Laguna | ||||
