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| H | Rayo Vallecano | - | Real Betis | 1:2 (1:1) | ||
| R | Real Betis | - | Rayo Vallecano | 1:1 (0:0) | ||
| H: 09.02.2022 21:00 | R: 03.03.2022 21:00 | Sieger: Real Betis | ||||
| H | Athletic Bilbao | - | Valencia CF | 1:1 (1:0) | ||
| R | Valencia CF | - | Athletic Bilbao | 1:0 (1:0) | ||
| H: 10.02.2022 21:30 | R: 02.03.2022 21:30 | Sieger: Valencia CF | ||||
