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| U | PAOK Saloniki | - | KAA Gent | 1:0 (0:0) | ||
| R | KAA Gent | - | PAOK Saloniki | 1:2 (1:1) | ||
| U: 10.03.2022 18:45 | R: 17.03.2022 21:00 | Winnaars: PAOK Saloniki | ||||
| U | Vitesse | - | AS Roma | 0:1 (0:1) | ||
| R | AS Roma | - | Vitesse | 1:1 (0:0) | ||
| U: 10.03.2022 18:45 | R: 17.03.2022 21:00 | Winnaars: AS Roma | ||||
| U | Slavia Praag | - | LASK | 4:1 (2:0) | ||
| R | LASK | - | Slavia Praag | 4:3 (1:2) | ||
| U: 10.03.2022 18:45 | R: 17.03.2022 21:00 | Winnaars: Slavia Praag | ||||
| U | Partizan | - | Feyenoord | 2:5 (1:1) | ||
| R | Feyenoord | - | Partizan | 3:1 (1:0) | ||
| U: 10.03.2022 18:45 | R: 17.03.2022 21:00 | Winnaars: Feyenoord | ||||
| U | Olympique Marseille | - | FC Basel 1893 | 2:1 (1:0) | ||
| R | FC Basel 1893 | - | Olympique Marseille | 1:2 (0:0) | ||
| U: 10.03.2022 21:00 | R: 17.03.2022 18:45 | Winnaars: Olympique Marseille | ||||
| U | Leicester City | - | Stade Rennais | 2:0 (1:0) | ||
| R | Stade Rennais | - | Leicester City | 2:1 (1:0) | ||
| U: 10.03.2022 21:00 | R: 17.03.2022 18:45 | Winnaars: Leicester City | ||||
| U | PSV | - | FC Kopenhagen | 4:4 (1:3) | ||
| R | FC Kopenhagen | - | PSV | 0:4 (0:2) | ||
| U: 10.03.2022 21:00 | R: 17.03.2022 18:45 | Winnaars: PSV | ||||
| U | FK Bodø/Glimt | - | AZ Alkmaar | 2:1 (1:0) | ||
| R | AZ Alkmaar | - | FK Bodø/Glimt | 2:2 (2:1, 2:1) n.v. | ||
| U: 10.03.2022 21:00 | R: 17.03.2022 18:45 | Winnaars: FK Bodø/Glimt | ||||
