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| 16/01/2021 | 11:00 | Peña Deportiva | - | Real Valladolid | 1:4 (1:0, 1:1) aet | |
| 11:00 | UD Almería | - | CD Alavés | 5:0 (3:0) | ||
| 15:00 | Girona FC | - | Cádiz CF | 2:0 (0:0) | ||
| 15:00 | Rayo Vallecano | - | Elche CF | 2:0 (1:0) | ||
| 17:00 | CF Fuenlabrada | - | Levante UD | 2:4 (0:1, 1:1, 1:1) pso | ||
| 19:00 | CD Leganés | - | Sevilla FC | 0:1 (0:0, 0:0) aet | ||
| 17/01/2021 | 11:00 | Málaga CF | - | Granada CF | 1:2 (0:2) | |
| 11:00 | Espanyol Barcelona | - | CA Osasuna | 0:2 (0:2) | ||
| 15:00 | CDA Navalcarnero | - | SD Eibar | 3:1 (1:1) | ||
| 15:00 | Sporting Gijón | - | Real Betis | 0:2 (0:2) | ||
| 17:00 | AD Alcorcón | - | Valencia CF | 0:2 (0:1) | ||
| 17:00 | CD Tenerife | - | Villarreal CF | 0:1 (0:0) | ||
| 20/01/2021 | 18:00 | Córdoba CF | - | Real Sociedad | 0:2 (0:0) | |
| 20:00 | CD Alcoyano | - | Real Madrid | 2:1 (0:1, 1:1) aet | ||
| 21/01/2021 | 18:00 | UD Ibiza | - | Athletic Club | 1:2 (1:0) | |
| 20:00 | UE Cornellà | - | FC Barcelona | 0:2 (0:0, 0:0) aet |
