| Date | Home | Away | Result |
|---|---|---|---|
| 04/01/22 20:00 | SD Ponferradina | Espanyol Barcelona | 2-4a.PSO |
| 05/01/22 15:00 | SD Eibar | RCD Mallorca | 1-2 |
| 05/01/22 15:00 | FC Cartagena | FC Valencia | 1-2 |
| 05/01/22 15:00 | CD Leganes | Real Sociedad | 2-3 |
| 05/01/22 18:30 | Linares Deportivo | FC Barcelona | 1-2 |
| 05/01/22 19:00 | CD Mirandes | Rayo Vallecano | 0-1 |
| 05/01/22 19:00 | Atletico Baleares | Celta Vigo | 2-1 |
| 05/01/22 19:00 | Real Valladolid | Real Betis Sevilla | 0-3 |
| 05/01/22 20:30 | CD Alcoyano | Real Madrid | 1-3 |
| 06/01/22 15:00 | FC Girona | CA Osasuna | 1-0 |
| 06/01/22 15:00 | CF Fuenlabrada | FC Cadiz | 0-1 |
| 06/01/22 17:00 | Sporting Gijon | FC Villarreal | 2-1 |
| 06/01/22 17:00 | Real Saragossa | FC Sevilla | 0-2 |
| 06/01/22 19:00 | UD Almeria | FC Elche | 1-2 |
| 06/01/22 19:00 | Atletico Mancha Real | Athletic Bilbao | 0-2 |
| 06/01/22 20:30 | CF Rayo Majadahonda | Atletico Madrid | 0-5 |