| 13. Round | 17/10/2021 | CF Pachuca | - | Santos Laguna | 1:1 | ||||
| 14. Round | 20/10/2021 | CF América | - | Santos Laguna | 2:1 | ||||
| 15. Round | 25/10/2021 | Santos Laguna | - | Deportivo Toluca | 2:2 |  |
|||
| 16. Round | 30/10/2021 | Gallos Blancos | - | Santos Laguna | 2:3 |  |
|||
| 11. Round | 05/11/2021 | Pumas UNAM | - | Santos Laguna | 0:3 | ||||
| 17. Round | 08/11/2021 | Santos Laguna | - | Atlético San Luis | 0:0 |
Ecuador
Spain