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| H (Match allé) | Iztapa | - | Comunicaciones | 0:0 (0:0) | ||
| R (match retour) | Comunicaciones | - | Iztapa | 1:0 (1:0) | ||
| H (Match allé): 11.12.2021 19:00 | R (match retour): 19.12.2021 03:15 | vainqueur: Comunicaciones | ||||
| H (Match allé) | Sololá FC | - | Antigua GFC | 0:1 (0:0) | ||
| R (match retour) | Antigua GFC | - | Sololá FC | 5:1 (1:0) | ||
| H (Match allé): 11.12.2021 22:00 | R (match retour): 19.12.2021 01:00 | vainqueur: Antigua GFC | ||||
| H (Match allé) | Santa Lucía | - | Deportivo Malacateco | 1:0 (0:0) | ||
| R (match retour) | Deportivo Malacateco | - | Santa Lucía | 1:0 (0:0) | ||
| H (Match allé): 12.12.2021 22:00 | R (match retour): 19.12.2021 22:00 | |||||
| H (Match allé) | Xelaju MC | - | CSD Municipal | 0:1 (0:0) | ||
| R (match retour) | CSD Municipal | - | Xelaju MC | 0:1 (0:1) | ||
| H (Match allé): 13.12.2021 03:00 | R (match retour): 19.12.2021 18:00 | |||||
