| 1. Round | 10/01/2016 | Club León | - | Santos Laguna | 2:0 | ||||
| 2. Round | 16/01/2016 | Santos Laguna | - | Chiapas FC | 1:0 | ||||
| 3. Round | 23/01/2016 | Club Tijuana | - | Santos Laguna | 1:3 | ||||
| 4. Round | 30/01/2016 | Santos Laguna | - | Gallos Blancos | 2:0 |  |
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| 5. Round | 06/02/2016 | CF América | - | Santos Laguna | 2:0 | ||||
| 6. Round | 13/02/2016 | Santos Laguna | - | CF Monterrey | 1:2 | ||||
| 7. Round | 21/02/2016 | Pumas UNAM | - | Santos Laguna | 1:1 | ||||
| 8. Round | 28/02/2016 | Santos Laguna | - | Puebla FC | 1:1 | ||||
| 9. Round | 06/03/2016 | Atlas Guadalajara | - | Santos Laguna | 1:2 | ||||
| 10. Round | 12/03/2016 | Santos Laguna | - | CF Pachuca | 3:2 | ||||
| 11. Round | 20/03/2016 | Dorados de Sinaloa | - | Santos Laguna | 3:1 | ||||
| 12. Round | 02/04/2016 | Deportivo Toluca | - | Santos Laguna | 0:0 | ||||
| 13. Round | 09/04/2016 | Santos Laguna | - | CD Veracruz | 2:0 | ||||
| 14. Round | 16/04/2016 | Cruz Azul | - | Santos Laguna | 0:1 | ||||
| 15. Round | 24/04/2016 | Santos Laguna | - | UANL Tigres | 2:1 | |
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| 16. Round | 01/05/2016 | Monarcas Morelia | - | Santos Laguna | 3:2 | ||||
| 17. Round | 07/05/2016 | Santos Laguna | - | Deportivo Guadalajara | 0:1 |
Chile
Spain