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| U | Deportivo Toluca | - | CF América | 0:1 (0:0) | ||
| R | CF América | - | Deportivo Toluca | 4:0 (1:0) | ||
| U: 04.05.2022 16:00 | R: 07.05.2022 16:30 | Winnaars: CF América | ||||
| U | Deportivo Guadalajara | - | Club Tijuana | 0:2 (0:1) | ||
| R | Club Tijuana | - | Deportivo Guadalajara | 1:0 (1:0) | ||
| U: 05.05.2022 16:00 | R: 09.05.2022 04:00 | Winnaars: Club Tijuana | ||||
| U | Santos Laguna | - | Club León | 1:0 (0:0) | ||
| R | Club León | - | Santos Laguna | 5:2 (2:0) | ||
| U: 05.05.2022 18:00 | R: 08.05.2022 16:00 | Winnaars: Club León | ||||
| U | UANL Tigres | - | CF Pachuca | 4:2 (2:0) | ||
| R | CF Pachuca | - | UANL Tigres | 1:0 (1:0) | ||
| U: 05.05.2022 18:00 | R: 08.05.2022 19:00 | Winnaars: UANL Tigres | ||||
