| 1. Round | 25/07/2010 | Atlante | - | Santos Laguna | 1:4 | ||||
| 2. Round | 01/08/2010 | Santos Laguna | - | Pumas UNAM | 4:0 |  |
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| 3. Round | 08/08/2010 | CF Pachuca | - | Santos Laguna | 0:3 | ||||
| 4. Round | 15/08/2010 | Santos Laguna | - | Jaguares Chiapas | 1:0 | ||||
| 5. Round | 22/08/2010 | UANL Tigres | - | Santos Laguna | 1:0 | ||||
| 6. Round | 29/08/2010 | Santos Laguna | - | Atlas Guadalajara | 3:1 | ||||
| 8. Round | 19/09/2010 | Santos Laguna | - | Club Necaxa | 2:1 |  |
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| 9. Round | 26/09/2010 | CF América | - | Santos Laguna | 3:2 | ||||
| 10. Round | 03/10/2010 | Santos Laguna | - | Deportivo Toluca | 2:0 | ||||
| 12. Round | 16/10/2010 | Cruz Azul | - | Santos Laguna | 3:0 | ||||
| 13. Round | 24/10/2010 | Santos Laguna | - | CF Monterrey | 1:2 | |
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| 14. Round | 28/10/2010 | Puebla FC | - | Santos Laguna | 0:1 | ||||
| 15. Round | 31/10/2010 | Santos Laguna | - | Deportivo Guadalajara | 1:1 | ||||
| 16. Round | 06/11/2010 | Club San Luis | - | Santos Laguna | 1:1 | |
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| 17. Round | 14/11/2010 | Santos Laguna | - | Estudiantes Tecos | 1:0 |
Panama
Mexico