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