*Olympique Marseille 4-2 FC Basel
| 17.03.2022 | FC Basel | 1-2 | Olympique Marseille | |
| 10.03.2022 | Olympique Marseille | 2-1 | FC Basel | |
*PSV Eindhoven 8-4 FC København
| 17.03.2022 | FC København | 0-4 | PSV Eindhoven | |
| 10.03.2022 | PSV Eindhoven | 4-4 | FC København | |
FK Partizan 3-8 Feyenoord *
| 17.03.2022 | Feyenoord | 3-1 | FK Partizan | |
| 10.03.2022 | FK Partizan | 2-5 | Feyenoord | |
*FK Bodo/Glimt 4-3 AZ Alkmaar
| 17.03.2022 | AZ Alkmaar | 2-2 AET | FK Bodo/Glimt | |
| 10.03.2022 | FK Bodo/Glimt | 2-1 | AZ Alkmaar | |
*PAOK Salonica 3-1 KAA Gent
| 17.03.2022 | KAA Gent | 1-2 | PAOK Salonica | |
| 10.03.2022 | PAOK Salonica | 1-0 | KAA Gent | |
*Slavia Praha 7-5 LASK Linz
| 17.03.2022 | LASK Linz | 4-3 | Slavia Praha | |
| 10.03.2022 | Slavia Praha | 4-1 | LASK Linz | |
*Leicester City 3-2 Stade Rennais
| 17.03.2022 | Stade Rennais | 2-1 | Leicester City | |
| 10.03.2022 | Leicester City | 2-0 | Stade Rennais | |
Vitesse Arnhem 1-2 AS Roma *
| 17.03.2022 | AS Roma | 1-1 | Vitesse Arnhem | |
| 10.03.2022 | Vitesse Arnhem | 0-1 | AS Roma | |