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| H | Feyenoord | - | Slavia Praha | 3:3 (1:1) | ||
| R | Slavia Praha | - | Feyenoord | 1:3 (1:1) | ||
| H: 07.04.2022 18:45 | R: 14.04.2022 21:00 | Sieger: Feyenoord | ||||
| H | FK Bodø/Glimt | - | AS Roma | 2:1 (0:1) | ||
| R | AS Roma | - | FK Bodø/Glimt | 4:0 (3:0) | ||
| H: 07.04.2022 21:00 | R: 14.04.2022 21:00 | Sieger: AS Roma | ||||
| H | Olympique Marseille | - | PAOK Saloniki | 2:1 (2:0) | ||
| R | PAOK Saloniki | - | Olympique Marseille | 0:1 (0:1) | ||
| H: 07.04.2022 21:00 | R: 14.04.2022 21:00 | Sieger: Olympique Marseille | ||||
| H | Leicester City | - | PSV Eindhoven | 0:0 (0:0) | ||
| R | PSV Eindhoven | - | Leicester City | 1:2 (1:0) | ||
| H: 07.04.2022 21:00 | R: 14.04.2022 18:45 | Sieger: Leicester City | ||||
