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| 1st(1st leg) | FC Porto | - | Olympique Lyonnais | 0:1 (0:0) | ||
| 2nd (2nd leg) | Olympique Lyonnais | - | FC Porto | 1:1 (1:1) | ||
| 1st(1st leg): 09/03/2022 17:45 | 2nd (2nd leg): 17/03/2022 20:00 | Winner: Olympique Lyonnais | ||||
| 1st(1st leg) | Real Betis | - | Eintracht Frankfurt | 1:2 (1:2) | ||
| 2nd (2nd leg) | Eintracht Frankfurt | - | Real Betis | 1:1 (0:0, 0:1) aet | ||
| 1st(1st leg): 09/03/2022 17:45 | 2nd (2nd leg): 17/03/2022 20:00 | Winner: Eintracht Frankfurt | ||||
| 1st(1st leg) | RB Leipzig | - | Spartak Moskva | dnp | ||
| 2nd (2nd leg) | Spartak Moskva | - | RB Leipzig | dnp | ||
| 1st(1st leg): 10/03/2022 | 2nd (2nd leg): 17/03/2022 | Winner: RB Leipzig | ||||
| 1st(1st leg) | Sevilla FC | - | West Ham United | 1:0 (0:0) | ||
| 2nd (2nd leg) | West Ham United | - | Sevilla FC | 2:0 (1:0, 1:0) aet | ||
| 1st(1st leg): 10/03/2022 17:45 | 2nd (2nd leg): 17/03/2022 20:00 | Winner: West Ham United | ||||
| 1st(1st leg) | Rangers FC | - | Crvena Zvezda | 3:0 (2:0) | ||
| 2nd (2nd leg) | Crvena Zvezda | - | Rangers FC | 2:1 (1:0) | ||
| 1st(1st leg): 10/03/2022 20:00 | 2nd (2nd leg): 17/03/2022 17:45 | Winner: Rangers FC | ||||
| 1st(1st leg) | Sporting Braga | - | AS Monaco | 2:0 (1:0) | ||
| 2nd (2nd leg) | AS Monaco | - | Sporting Braga | 1:1 (0:1) | ||
| 1st(1st leg): 10/03/2022 20:00 | 2nd (2nd leg): 17/03/2022 17:45 | Winner: Sporting Braga | ||||
| 1st(1st leg) | Atalanta | - | Bayer Leverkusen | 3:2 (2:1) | ||
| 2nd (2nd leg) | Bayer Leverkusen | - | Atalanta | 0:1 (0:0) | ||
| 1st(1st leg): 10/03/2022 20:00 | 2nd (2nd leg): 17/03/2022 17:45 | Winner: Atalanta | ||||
| 1st(1st leg) | FC Barcelona | - | Galatasaray | 0:0 (0:0) | ||
| 2nd (2nd leg) | Galatasaray | - | FC Barcelona | 1:2 (1:1) | ||
| 1st(1st leg): 10/03/2022 20:00 | 2nd (2nd leg): 17/03/2022 17:45 | Winner: FC Barcelona | ||||
