| 10 Sep 21 | r16        | Alianza FCAlianza FC | 1 - 0 | Once DeportivoOnce Deportiv |
| 30 Oct 21 | r16        | JocoroJocoro | 1 - 1 | Atlético MarteAtlético Mart |
| 30 Oct 21 | r16        | LimeñoLimeño | 2 - 2 | Isidro MetapánIsidro Metapá |
| 30 Oct 21 | r16        | Platense Puerto CortésPlatense Puer | 0 - 0 | FASFAS |
| 31 Oct 21 | r16        | CD ÁguilaCD Águila | 2 - 0 | Santa Tecla FCSanta Tecla F |
| 31 Oct 21 | r16        | FirpoFirpo | 4 - 2 | ChalatenangoChalatenango |
| 10 Apr 22 | r16        | Santa Tecla FCSanta Tecla F | 1 - 1 | FASFAS |
| 10 Apr 22 | r16        | Isidro MetapánIsidro Metapá | 2 - 2 | Once DeportivoOnce Deportiv |
| 10 Apr 22 | r16        | ChalatenangoChalatenango | 1 - 2 | Platense Puerto CortésPlatense Puer |
| 10 Apr 22 | r16        | LimeñoLimeño | 2 - 2 | JocoroJocoro |
| 10 Apr 22 | r16        | Atlético MarteAtlético Mart | 0 - 4 | CD ÁguilaCD Águila |
| 10 Apr 22 | r16        | FirpoFirpo | 0 - 1 | Alianza FCAlianza FC |