| 1. Round | 29/07/2021 | CS Herediano | - | Guadalupe | 0:1 | ||||
| 2. Round | 01/08/2021 | Guadalupe | - | AD San Carlos | 1:1 | ||||
| 3. Round | 07/08/2021 | AD Guanacasteca | - | Guadalupe | 0:1 | ||||
| 4. Round | 11/08/2021 | Guadalupe | - | Deportivo Saprissa | 1:1 | ||||
| 5. Round | 15/08/2021 | Municipal Pérez Zeledón | - | Guadalupe | 1:1 | ||||
| 6. Round | 18/08/2021 | Guadalupe | - | Sporting FC | 2:2 | ||||
| 7. Round | 25/08/2021 | CS Cartaginés | - | Guadalupe | 0:1 | ||||
| 13. Round | 26/09/2021 | AD San Carlos | - | Guadalupe | 4:2 | ||||
| 14. Round | 01/10/2021 | Guadalupe | - | AD Guanacasteca | 1:1 | ||||
| 16. Round | 17/10/2021 | Guadalupe | - | Municipal Pérez Zeledón | 0:1 | ||||
| 17. Round | 23/10/2021 | Sporting FC | - | Guadalupe | 2:0 |  |
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| 18. Round | 27/10/2021 | Guadalupe | - | CS Cartaginés | 1:1 | |
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| 19. Round | 30/10/2021 | Guadalupe | - | Jicaral | 2:0 | ||||
| 20. Round | 21/11/2021 | Municipal Grecia | - | Guadalupe | 0:0 | ||||
| 21. Round | 25/11/2021 | LD Alajuelense | - | Guadalupe | 1:0 | ||||
| 22. Round | 28/11/2021 | Guadalupe | - | Santos de Guápiles | 0:5 |
Costa Rica