| 3. Round | 06/02/2022 | Real España | - | Motagua | 1:2 | ||||
| 4. Round | 11/02/2022 | Marathón | - | Real España | 2:0 | ||||
| 5. Round | 13/02/2022 | Real España | - | Real Sociedad | 4:1 | ||||
| 6. Round | 20/02/2022 | Olimpia | - | Real España | 1:3 | ||||
| 7. Round | 27/02/2022 | Real España | - | Honduras Progreso | 3:0 | ||||
| 8. Round | 03/03/2022 | Real España | - | Lobos UPNFM | 1:0 | ||||
| 9. Round | 06/03/2022 | Vida | - | Real España | 0:1 | ||||
| 10. Round | 13/03/2022 | Motagua | - | Real España | 0:2 | ||||
| 15. Round | 14/04/2022 | Lobos UPNFM | - | Real España | 0:2 | ||||
| 16. Round | 21/04/2022 | Real España | - | Victoria | 3:1 | ||||
| 17. Round | 24/04/2022 | Honduras Progreso | - | Real España | 1:1 | ||||
| 18. Round | 01/05/2022 | Real España | - | Vida | 1:4 |
Honduras