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| 1st(1st leg) | Santos de Guápiles | - | Forge FC | 3:1 (2:1) | ||
| 2nd (2nd leg) | Forge FC | - | Santos de Guápiles | 3:0 (1:0) | ||
| 1st(1st leg): 20/10/2021 23:00 | 2nd (2nd leg): 03/11/2021 00:00 | Winner: Forge FC | ||||
| 1st(1st leg) | Deportivo Saprissa | - | Comunicaciones | 4:3 (2:2) | ||
| 2nd (2nd leg) | Comunicaciones | - | Deportivo Saprissa | 2:1 (1:1) | ||
| 1st(1st leg): 22/10/2021 01:00 | 2nd (2nd leg): 04/11/2021 01:00 | Winner: Comunicaciones | ||||
| 1st(1st leg) | Marathón | - | Motagua | 0:2 (0:1) | ||
| 2nd (2nd leg) | Motagua | - | Marathón | 2:0 (0:0) | ||
| 1st(1st leg): 22/10/2021 03:00 | 2nd (2nd leg): 03/11/2021 02:15 | Winner: Motagua | ||||
