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| 1st(1st leg) | PAOK Saloniki | - | KAA Gent | 1:0 (0:0) | ||
| 2nd (2nd leg) | KAA Gent | - | PAOK Saloniki | 1:2 (1:1) | ||
| 1st(1st leg): 10/03/2022 17:45 | 2nd (2nd leg): 17/03/2022 20:00 | Winner: PAOK Saloniki | ||||
| 1st(1st leg) | Vitesse | - | AS Roma | 0:1 (0:1) | ||
| 2nd (2nd leg) | AS Roma | - | Vitesse | 1:1 (0:0) | ||
| 1st(1st leg): 10/03/2022 17:45 | 2nd (2nd leg): 17/03/2022 20:00 | Winner: AS Roma | ||||
| 1st(1st leg) | Slavia Praha | - | LASK | 4:1 (2:0) | ||
| 2nd (2nd leg) | LASK | - | Slavia Praha | 4:3 (1:2) | ||
| 1st(1st leg): 10/03/2022 17:45 | 2nd (2nd leg): 17/03/2022 20:00 | Winner: Slavia Praha | ||||
| 1st(1st leg) | Partizan | - | Feyenoord | 2:5 (1:1) | ||
| 2nd (2nd leg) | Feyenoord | - | Partizan | 3:1 (1:0) | ||
| 1st(1st leg): 10/03/2022 17:45 | 2nd (2nd leg): 17/03/2022 20:00 | Winner: Feyenoord | ||||
| 1st(1st leg) | Olympique Marseille | - | FC Basel 1893 | 2:1 (1:0) | ||
| 2nd (2nd leg) | FC Basel 1893 | - | Olympique Marseille | 1:2 (0:0) | ||
| 1st(1st leg): 10/03/2022 20:00 | 2nd (2nd leg): 17/03/2022 17:45 | Winner: Olympique Marseille | ||||
| 1st(1st leg) | Leicester City | - | Stade Rennais | 2:0 (1:0) | ||
| 2nd (2nd leg) | Stade Rennais | - | Leicester City | 2:1 (1:0) | ||
| 1st(1st leg): 10/03/2022 20:00 | 2nd (2nd leg): 17/03/2022 17:45 | Winner: Leicester City | ||||
| 1st(1st leg) | PSV Eindhoven | - | FC København | 4:4 (1:3) | ||
| 2nd (2nd leg) | FC København | - | PSV Eindhoven | 0:4 (0:2) | ||
| 1st(1st leg): 10/03/2022 20:00 | 2nd (2nd leg): 17/03/2022 17:45 | Winner: PSV Eindhoven | ||||
| 1st(1st leg) | FK Bodø/Glimt | - | AZ Alkmaar | 2:1 (1:0) | ||
| 2nd (2nd leg) | AZ Alkmaar | - | FK Bodø/Glimt | 2:2 (2:1, 2:1) aet | ||
| 1st(1st leg): 10/03/2022 20:00 | 2nd (2nd leg): 17/03/2022 17:45 | Winner: FK Bodø/Glimt | ||||
