| 1. Round | 27/07/2008 | CF América | - | Santos Laguna | 3:2 |  |
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| 2. Round | 03/08/2008 | Santos Laguna | - | Pumas UNAM | 1:1 | ||||
| 3. Round | 10/08/2008 | Puebla FC | - | Santos Laguna | 0:0 | ||||
| 5. Round | 24/08/2008 | Deportivo Guadalajara | - | Santos Laguna | 3:5 |  |
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| 6. Round | 27/08/2008 | Santos Laguna | - | UAG Tecos | 2:0 | |
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| 7. Round | 30/08/2008 | CF Monterrey | - | Santos Laguna | 2:0 |  |
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| 10. Round | 28/09/2008 | Deportivo Toluca | - | Santos Laguna | 2:1 | |
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| 11. Round | 05/10/2008 | Santos Laguna | - | Monarcas Morelia | 1:0 | ||||
| 15. Round | 02/11/2008 | Santos Laguna | - | UANL Tigres | 1:1 | ||||
| 16. Round | 08/11/2008 | Club San Luis | - | Santos Laguna | 2:2 | ||||
| 17. Round | 16/11/2008 | Santos Laguna | - | Atlante | 0:0 | |
Mexico