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| H (Match allé) | Motagua | - | Real España | 1:1 (0:1) | ||
| R (match retour) | Real España | - | Motagua | 2:0 (0:0) | ||
| H (Match allé): 05.12.2021 02:00 | R (match retour): 12.12.2021 02:00 | vainqueur: Real España | ||||
| H (Match allé) | Olimpia | - | Vida | 2:0 (0:0) | ||
| R (match retour) | Vida | - | Olimpia | 2:1 (2:1) | ||
| H (Match allé): 05.12.2021 23:00 | R (match retour): 12.12.2021 02:30 | vainqueur: Olimpia | ||||
