| 10/09/2021 | Real Sporting vs. CD Leganes | ||
| 11/09/2021 | Real Sociedad B vs. SD Eibar | ||
| 11/09/2021 | SD Amorebieta vs. Burgos CF | ||
| 11/09/2021 | UD Las Palmas vs. UD Ibiza | ||
| 11/09/2021 | CD Mirandes vs. AD Alcorcon | ||
| 12/09/2021 | SD Ponferradina vs. UD Almeria | ||
| 12/09/2021 | CF Fuenlabrada vs. Saragosse | ||
| 12/09/2021 | Malaga vs. Girona FC | ||
| 12/09/2021 | Real Oviedo vs. FC Cartagena | ||
| 12/09/2021 | Valladolid vs. Tenerife | ||
| 13/09/2021 | CD Lugo vs. Huesca |