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| 1st(1st leg) | Santa Lucía | - | Comunicaciones | 0:3 (0:0) | ||
| 2nd (2nd leg) | Comunicaciones | - | Santa Lucía | 0:0 (0:0) | ||
| 1st(1st leg): 11/05/2022 18:00 | 2nd (2nd leg): 15/05/2022 01:00 | Winner: Comunicaciones | ||||
| 1st(1st leg) | Achuapa | - | CSD Municipal | 0:1 (0:1) | ||
| 2nd (2nd leg) | CSD Municipal | - | Achuapa | 2:0 (0:0) | ||
| 1st(1st leg): 11/05/2022 22:00 | 2nd (2nd leg): 14/05/2022 22:00 | Winner: CSD Municipal | ||||
| 1st(1st leg) | Cobán Imperial | - | Deportivo Malacateco | 0:0 (0:0) | ||
| 2nd (2nd leg) | Deportivo Malacateco | - | Cobán Imperial | 0:0 (0:0) | ||
| 1st(1st leg): 12/05/2022 22:00 | 2nd (2nd leg): 15/05/2022 20:00 | |||||
| 1st(1st leg) | Antigua GFC | - | Deportivo Guastatoya | 1:0 (1:0) | ||
| 2nd (2nd leg) | Deportivo Guastatoya | - | Antigua GFC | 2:0 (1:0) | ||
| 1st(1st leg): 13/05/2022 02:00 | 2nd (2nd leg): 15/05/2022 17:45 | Winner: Deportivo Guastatoya | ||||
