| 3. Round | 16/08/2021 | Managua FC | - | Real Estelí FC | 3:0 | ||||
| 9. Round | 26/09/2021 | Club Deportivo Ocotal | - | Real Estelí FC | 1:2 | ||||
| 10. Round | 02/10/2021 | H&H Export Sébaco | - | Real Estelí FC | 1:3 | ||||
| 8. Round | 07/10/2021 | Real Estelí FC | - | CD Walter Ferretti | 1:1 | ||||
| 11. Round | 11/10/2021 | Real Madriz | - | Real Estelí FC | 1:2 | ||||
| 12. Round | 17/10/2021 | Real Estelí FC | - | Managua FC | 1:0 | ||||
| 13. Round | 21/10/2021 | Real Estelí FC | - | Juventus Managua | 3:0 | ||||
| 14. Round | 24/10/2021 | ART Municipal Jalapa | - | Real Estelí FC | 2:1 |  |
|||
| 15. Round | 31/10/2021 | Real Estelí FC | - | Diriangén FC | 3:0 |  |
|||
| 16. Round | 04/11/2021 | UNAN Managua | - | Real Estelí FC | 3:3 | ||||
| 17. Round | 19/11/2021 | CD Walter Ferretti | - | Real Estelí FC | 4:0 | ||||
| 18. Round | 22/11/2021 | Real Estelí FC | - | Club Deportivo Ocotal | 4:0 |  |
Nicaragua