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| H | Cruz Azul | - | UANL Tigres | 0:4 (0:3) | ||
| R | UANL Tigres | - | Cruz Azul | 4:0 (1:0) | ||
| H: 03.12.2021 19:45 | R: 07.12.2021 02:00 | Sieger: UANL Tigres | ||||
| H | Santos Laguna | - | Atlas Guadalajara | 2:2 (0:0) | ||
| R | Atlas Guadalajara | - | Santos Laguna | 2:1 (1:1) | ||
| H: 04.12.2021 01:00 | R: 06.12.2021 19:00 | Sieger: Atlas Guadalajara | ||||
| H | CF América | - | Deportivo Guadalajara | 2:1 (2:0) | ||
| R | Deportivo Guadalajara | - | CF América | 0:0 (0:0) | ||
| H: 04.12.2021 03:00 | R: 07.12.2021 00:00 | Sieger: CF América | ||||
| H | Club Tijuana | - | CF Monterrey | 1:1 (1:0) | ||
| R | CF Monterrey | - | Club Tijuana | 1:1 (1:1) | ||
| H: 04.12.2021 04:30 | R: 07.12.2021 04:00 | |||||
