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| 04.01.2022 | 21:00 | SD Ponferradina | - | Espanyol Barcelona | 1:3 (0:1, 1:1, 1:1) tab | |
| 05.01.2022 | 16:00 | FC Cartagena | - | Valencia CF | 1:2 (0:1) | |
| 16:00 | SD Eibar | - | RCD Mallorca | 1:2 (1:0) | ||
| 16:00 | CD Leganés | - | Real Sociedad | 2:3 (0:2) | ||
| 19:30 | Linares Deportivo | - | FC Barcelona | 1:2 (1:0) | ||
| 20:00 | Atlético Baleares | - | RC Celta | 2:1 (1:0) | ||
| 20:00 | Real Valladolid | - | Real Betis | 0:3 (0:2) | ||
| 20:00 | CD Mirandés | - | Rayo Vallecano | 0:1 (0:0) | ||
| 21:30 | CD Alcoyano | - | Real Madrid | 1:3 (0:1) | ||
| 06.01.2022 | 16:00 | CF Fuenlabrada | - | Cádiz CF | 0:1 (0:0) | |
| 16:00 | Girona FC | - | CA Osasuna | 1:0 (1:0) | ||
| 18:00 | Sporting Gijón | - | Villarreal CF | 2:1 (0:0) | ||
| 18:00 | Real Zaragoza | - | Sevilla FC | 0:2 (0:1) | ||
| 20:00 | Atlético Mancha Real | - | Athletic Club | 0:2 (0:2) | ||
| 20:00 | UD Almería | - | Elche CF | 1:2 (1:0) | ||
| 21:30 | Rayo Majadahonda | - | Atlético Madrid | 0:5 (0:3) |
