| 10. Round | 19/09/2021 | FAS | - | Isidro Metapán | 3:0 |  |
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| 11. Round | 26/09/2021 | Isidro Metapán | - | AD Chalatenango | 1:4 | ||||
| 12. Round | 02/10/2021 | Atlético Marte | - | Isidro Metapán | 2:0 | ||||
| 13. Round | 17/10/2021 | Isidro Metapán | - | Santa Tecla FC | 1:1 | |
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| 14. Round | 21/10/2021 | CD Águila | - | Isidro Metapán | 4:0 | ||||
| 15. Round | 24/10/2021 | Isidro Metapán | - | Jocoro FC | 1:1 | ||||
| 16. Round | 30/10/2021 | Municipal Limeño | - | Isidro Metapán | 2:2 | ||||
| 17. Round | 03/11/2021 | Isidro Metapán | - | Platense Zacatecoluca | 1:0 | |
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| 19. Round | 14/11/2021 | Isidro Metapán | - | Luis Ángel Firpo | 2:1 | |
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| 20. Round | 18/11/2021 | Once Municipal | - | Isidro Metapán | 1:1 | ||||
| 21. Round | 21/11/2021 | Isidro Metapán | - | FAS | 1:2 | ||||
| 22. Round | 27/11/2021 | AD Chalatenango | - | Isidro Metapán | 1:0 | |
El Salvador