| September 11, 2021 | ||
| Villarreal | 18:30 | Alaves |
| Sevilla | 21:00 | Barcelona |
| October 16, 2021 | ||
| Levante | 18:30 | Getafe |
| Real Sociedad | 21:00 | Mallorca |
| October 17, 2021 | ||
| Granada | 02:00 | Atlético de Madrid |
| Real Madrid | 02:00 | Athletic Bilbao |
| Rayo Vallecano | 14:00 | Elche |
| Celta Vigo | 16:15 | Sevilla |
| Villarreal | 18:30 | Osasuna |
| Barcelona | 21:00 | Valencia |
| October 18, 2021 | ||
| Alaves | 19:00 | Real Betis |
| Espanyol | 21:00 | Cadiz |
| October 22, 2021 | ||
| Osasuna | 21:00 | Granada |
| October 23, 2021 | ||
| Valencia | 14:00 | Mallorca |
| Cadiz | 16:15 | Alaves |
| Elche | 18:30 | Espanyol |
| Athletic Bilbao | 21:00 | Villarreal |
