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| 1st(1st leg) | Iztapa | - | Comunicaciones | 0:0 (0:0) | ||
| 2nd (2nd leg) | Comunicaciones | - | Iztapa | 1:0 (1:0) | ||
| 1st(1st leg): 11/12/2021 18:00 | 2nd (2nd leg): 19/12/2021 02:15 | Winner: Comunicaciones | ||||
| 1st(1st leg) | Sololá FC | - | Antigua GFC | 0:1 (0:0) | ||
| 2nd (2nd leg) | Antigua GFC | - | Sololá FC | 5:1 (1:0) | ||
| 1st(1st leg): 11/12/2021 21:00 | 2nd (2nd leg): 19/12/2021 00:00 | Winner: Antigua GFC | ||||
| 1st(1st leg) | Santa Lucía | - | Deportivo Malacateco | 1:0 (0:0) | ||
| 2nd (2nd leg) | Deportivo Malacateco | - | Santa Lucía | 1:0 (0:0) | ||
| 1st(1st leg): 12/12/2021 21:00 | 2nd (2nd leg): 19/12/2021 21:00 | |||||
| 1st(1st leg) | Xelaju MC | - | CSD Municipal | 0:1 (0:0) | ||
| 2nd (2nd leg) | CSD Municipal | - | Xelaju MC | 0:1 (0:1) | ||
| 1st(1st leg): 13/12/2021 02:00 | 2nd (2nd leg): 19/12/2021 17:00 | |||||
