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| H (Match allé) | Marathón | - | Olimpia | 1:0 (1:0) | ||
| R (match retour) | Olimpia | - | Marathón | 3:0 (1:0) | ||
| H (Match allé): 19.11.2021 02:00 | R (match retour): 21.11.2021 23:00 | vainqueur: Olimpia | ||||
| H (Match allé) | Lobos UPNFM | - | Motagua | 1:2 (0:0) | ||
| R (match retour) | Motagua | - | Lobos UPNFM | 3:1 (2:1) | ||
| H (Match allé): 19.11.2021 02:05 | R (match retour): 21.11.2021 02:10 | vainqueur: Motagua | ||||
