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| 1st(1st leg) | Jocoro FC | - | Alianza | 2:3 (1:2) | ||
| 2nd (2nd leg) | Alianza | - | Jocoro FC | 1:0 (0:0) | ||
| 1st(1st leg): 01/12/2021 21:00 | 2nd (2nd leg): 05/12/2021 21:00 | Winner: Alianza | ||||
| 1st(1st leg) | Platense Zacatecoluca | - | Luis Ángel Firpo | 2:2 (2:1) | ||
| 2nd (2nd leg) | Luis Ángel Firpo | - | Platense Zacatecoluca | 1:2 (1:1) | ||
| 1st(1st leg): 01/12/2021 21:15 | 2nd (2nd leg): 05/12/2021 21:15 | Winner: Platense Zacatecoluca | ||||
| 1st(1st leg) | CD Águila | - | Once Municipal | 1:1 (0:1) | ||
| 2nd (2nd leg) | Once Municipal | - | CD Águila | 4:3 (0:0, 0:0, 0:0) pso | ||
| 1st(1st leg): 02/12/2021 01:00 | 2nd (2nd leg): 05/12/2021 21:00 | Winner: Once Municipal | ||||
| 1st(1st leg) | AD Chalatenango | - | FAS | 0:0 (0:0) | ||
| 2nd (2nd leg) | FAS | - | AD Chalatenango | 2:4 (1:0, 1:1) pso | ||
| 1st(1st leg): 03/12/2021 00:30 | 2nd (2nd leg): 05/12/2021 21:00 | Winner: AD Chalatenango | ||||
