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| 1st(1st leg) | PSV Eindhoven | - | Maccabi Tel Aviv | 1:0 (1:0) | ||
| 2nd (2nd leg) | Maccabi Tel Aviv | - | PSV Eindhoven | 1:1 (0:0) | ||
| 1st(1st leg): 17/02/2022 17:45 | 2nd (2nd leg): 24/02/2022 17:45 | Winner: PSV Eindhoven | ||||
| 1st(1st leg) | Fenerbahçe | - | Slavia Praha | 2:3 (0:1) | ||
| 2nd (2nd leg) | Slavia Praha | - | Fenerbahçe | 3:2 (2:1) | ||
| 1st(1st leg): 17/02/2022 17:45 | 2nd (2nd leg): 24/02/2022 20:00 | Winner: Slavia Praha | ||||
| 1st(1st leg) | FC Midtjylland | - | PAOK Saloniki | 1:0 (1:0) | ||
| 2nd (2nd leg) | PAOK Saloniki | - | FC Midtjylland | 5:3 (2:0, 2:1, 2:1) pso | ||
| 1st(1st leg): 17/02/2022 17:45 | 2nd (2nd leg): 24/02/2022 20:00 | Winner: PAOK Saloniki | ||||
| 1st(1st leg) | Rapid Wien | - | Vitesse | 2:1 (2:0) | ||
| 2nd (2nd leg) | Vitesse | - | Rapid Wien | 2:0 (2:0) | ||
| 1st(1st leg): 17/02/2022 17:45 | 2nd (2nd leg): 24/02/2022 20:00 | Winner: Vitesse | ||||
| 1st(1st leg) | Olympique Marseille | - | Qarabağ FK | 3:1 (2:0) | ||
| 2nd (2nd leg) | Qarabağ FK | - | Olympique Marseille | 0:3 (0:1) | ||
| 1st(1st leg): 17/02/2022 20:00 | 2nd (2nd leg): 24/02/2022 17:45 | Winner: Olympique Marseille | ||||
| 1st(1st leg) | Leicester City | - | Randers FC | 4:1 (1:1) | ||
| 2nd (2nd leg) | Randers FC | - | Leicester City | 1:3 (0:1) | ||
| 1st(1st leg): 17/02/2022 20:00 | 2nd (2nd leg): 24/02/2022 17:45 | Winner: Leicester City | ||||
| 1st(1st leg) | Celtic FC | - | FK Bodø/Glimt | 1:3 (0:1) | ||
| 2nd (2nd leg) | FK Bodø/Glimt | - | Celtic FC | 2:0 (1:0) | ||
| 1st(1st leg): 17/02/2022 20:00 | 2nd (2nd leg): 24/02/2022 17:45 | Winner: FK Bodø/Glimt | ||||
| 1st(1st leg) | AC Sparta Praha | - | Partizan | 0:1 (0:0) | ||
| 2nd (2nd leg) | Partizan | - | AC Sparta Praha | 2:1 (2:0) | ||
| 1st(1st leg): 17/02/2022 20:00 | 2nd (2nd leg): 24/02/2022 17:45 | Winner: Partizan | ||||
