| 3. Round | 15/08/2021 | Lobos UPNFM | - | Honduras Progreso | 3:0 |  |
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| 4. Round | 22/08/2021 | Lobos UPNFM | - | Platense | 3:0 | |
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| 5. Round | 26/08/2021 | Real España | - | Lobos UPNFM | 5:3 | |
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| 6. Round | 31/08/2021 | Motagua | - | Lobos UPNFM | 0:0 | ||||
| 7. Round | 04/09/2021 | Lobos UPNFM | - | Victoria | 3:0 | |
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| 8. Round | 12/09/2021 | Lobos UPNFM | - | Olimpia | 0:0 | ||||
| 9. Round | 15/09/2021 | Lobos UPNFM | - | Real Sociedad | 2:0 | ||||
| 10. Round | 19/09/2021 | Lobos UPNFM | - | Motagua | 2:2 | ||||
| 11. Round | 26/09/2021 | Platense | - | Lobos UPNFM | 2:3 | |
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| 12. Round | 03/10/2021 | Lobos UPNFM | - | Marathón | 1:1 | ||||
| 13. Round | 10/10/2021 | Lobos UPNFM | - | Vida | 0:0 | ||||
| 14. Round | 17/10/2021 | Honduras Progreso | - | Lobos UPNFM | 0:1 | |
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| 15. Round | 24/10/2021 | Lobos UPNFM | - | Real España | 1:2 | |
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| 16. Round | 27/10/2021 | Real Sociedad | - | Lobos UPNFM | 0:3 | ||||
| 17. Round | 31/10/2021 | Olimpia | - | Lobos UPNFM | 2:1 |  |
Honduras