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| 17.11.2021 | 15:00 | Nalón CF | - | SD Solares | 3:4 (0:1, 1:1, 1:1) i.E. | |
| 19:00 | CD Utrillas | - | CD Injerto | 2:0 (1:0) | ||
| 19:30 | CD Aldeano | - | Unami CP | 1:3 (0:2) | ||
| 19:30 | Victoria CF | - | CD Hernani | 1:0 (0:0) | ||
| 20:00 | CF San Agustín | - | Mora CF | 6:2 (4:1) | ||
| 20:30 | CFJ Mollerussa | - | Penya Independent | 1:0 (0:0) | ||
| 20:30 | CFI Alicante | - | Ceuta 6 de Junio | 7:1 (2:0) | ||
| 20:30 | CD Villa de Fortuna | - | Atlético Espeleño | 1:0 (0:0) | ||
| 21:00 | Huracán Melilla | - | Atarfe Industrial CF | 2:1 (1:1) | ||
| 21:30 | CD Laguna | - | CF Jaraíz | 4:1 (3:1) |
