| 05/01/21 16:00 | UD Ibiza Eivissa | Celta Vigo | 5-2 |
| 05/01/21 16:00 | Cordoba CF | FC Getafe | 1-0 |
| 05/01/21 18:00 | Zamora CF | FC Villarreal | 1-4 |
| 05/01/21 18:00 | Linares Deportivo | FC Sevilla | 0-2 |
| 05/01/21 20:00 | AD Alcorcon | Real Saragossa | 2-1 |
| 05/01/21 20:15 | Marbella FC | Real Valladolid | 2-3a.e.t |
| 06/01/21 11:00 | CF La Nucia | FC Elche | 0-1 |
| 06/01/21 11:00 | Club Portugalete | UD Levante | 1-2 |
| 06/01/21 11:00 | CD Numancia | UD Almeria | 1-2 |
| 06/01/21 12:00 | UD Socuellamos | CD Leganes | 0-2 |
| 06/01/21 16:00 | CD Artistico Navalcarnero | UD Las Palmas | 1-0 |
| 06/01/21 16:00 | Club Haro Deportivo | Rayo Vallecano | 1-3 |
| 06/01/21 16:00 | Cultural y Deportiva Leonesa | FC Granada | 1-2a.e.t |
| 06/01/21 16:00 | Union Mutilvera | Real Betis Sevilla | 1-3 |
| 06/01/21 17:00 | UE Cornella | Atletico Madrid | 1-0 |
| 06/01/21 18:00 | Deportivo La Coruna | Deportivo Alaves | 0-1 |
| 06/01/21 18:00 | Olot | CA Osasuna | 0-3 |
| 06/01/21 18:00 | Burgos CF | Espanyol Barcelona | 0-2 |
| 06/01/21 19:00 | CD Castellon | CD Teneriffa | 0-2 |
| 06/01/21 20:00 | CF Fuenlabrada | RCD Mallorca | 9-8a.PSO |
| 06/01/21 20:00 | FC Malaga | Real Oviedo | 1-0a.e.t |
| 07/01/21 18:00 | CF Pontevedra | FC Cadiz | 4-5a.PSO |
| 07/01/21 18:00 | SD Amorebieta | Sporting Gijon | 0-1 |
| 07/01/21 18:00 | Deportiva Santa Eulalia del Rio | CD Sabadell | 2-0a.PSO |
| 07/01/21 18:00 | FC Girona | CD Lugo | 2-1a.e.t |
| 07/01/21 18:00 | Yeclano Deportivo | FC Valencia | 1-4 |
| 07/01/21 20:00 | Las Rozas CF | SD Eibar | 3-4a.e.t |
| 07/01/21 20:00 | CD Alcoyano | SD Huesca | 2-1 |
