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| 1st(1st leg) | FC Barcelona | - | SSC Napoli | 1:1 (0:1) | ||
| 2nd (2nd leg) | SSC Napoli | - | FC Barcelona | 2:4 (1:3) | ||
| 1st(1st leg): 17/02/2022 17:45 | 2nd (2nd leg): 24/02/2022 20:00 | Winner: FC Barcelona | ||||
| 1st(1st leg) | Zenit St. Petersburg | - | Real Betis | 2:3 (2:3) | ||
| 2nd (2nd leg) | Real Betis | - | Zenit St. Petersburg | 0:0 (0:0) | ||
| 1st(1st leg): 17/02/2022 17:45 | 2nd (2nd leg): 24/02/2022 20:00 | Winner: Real Betis | ||||
| 1st(1st leg) | Borussia Dortmund | - | Rangers FC | 2:4 (0:2) | ||
| 2nd (2nd leg) | Rangers FC | - | Borussia Dortmund | 2:2 (1:2) | ||
| 1st(1st leg): 17/02/2022 17:45 | 2nd (2nd leg): 24/02/2022 20:00 | Winner: Rangers FC | ||||
| 1st(1st leg) | FC Sheriff | - | Sporting Braga | 2:0 (1:0) | ||
| 2nd (2nd leg) | Sporting Braga | - | FC Sheriff | 3:2 (2:0, 2:0, 2:0) pso | ||
| 1st(1st leg): 17/02/2022 17:45 | 2nd (2nd leg): 24/02/2022 20:00 | Winner: Sporting Braga | ||||
| 1st(1st leg) | Sevilla FC | - | Dinamo Zagreb | 3:1 (3:1) | ||
| 2nd (2nd leg) | Dinamo Zagreb | - | Sevilla FC | 1:0 (0:0) | ||
| 1st(1st leg): 17/02/2022 20:00 | 2nd (2nd leg): 24/02/2022 17:45 | Winner: Sevilla FC | ||||
| 1st(1st leg) | Atalanta | - | Olympiakos Piraeus | 2:1 (0:1) | ||
| 2nd (2nd leg) | Olympiakos Piraeus | - | Atalanta | 0:3 (0:1) | ||
| 1st(1st leg): 17/02/2022 20:00 | 2nd (2nd leg): 24/02/2022 17:45 | Winner: Atalanta | ||||
| 1st(1st leg) | RB Leipzig | - | Real Sociedad | 2:2 (1:1) | ||
| 2nd (2nd leg) | Real Sociedad | - | RB Leipzig | 1:3 (0:1) | ||
| 1st(1st leg): 17/02/2022 20:00 | 2nd (2nd leg): 24/02/2022 17:45 | Winner: RB Leipzig | ||||
| 1st(1st leg) | FC Porto | - | Lazio Roma | 2:1 (1:1) | ||
| 2nd (2nd leg) | Lazio Roma | - | FC Porto | 2:2 (1:1) | ||
| 1st(1st leg): 17/02/2022 20:00 | 2nd (2nd leg): 24/02/2022 17:45 | Winner: FC Porto | ||||
