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| 1st(1st leg) | RB Salzburg | - | Brøndby IF | 2:1 (0:1) | ||
| 2nd (2nd leg) | Brøndby IF | - | RB Salzburg | 1:2 (0:2) | ||
| 1st(1st leg): 17/08/2021 20:00 | 2nd (2nd leg): 25/08/2021 20:00 | Winner: RB Salzburg | ||||
| 1st(1st leg) | FC Sheriff | - | Dinamo Zagreb | 3:0 (1:0) | ||
| 2nd (2nd leg) | Dinamo Zagreb | - | FC Sheriff | 0:0 (0:0) | ||
| 1st(1st leg): 17/08/2021 20:00 | 2nd (2nd leg): 25/08/2021 20:00 | Winner: FC Sheriff | ||||
| 1st(1st leg) | AS Monaco | - | Shakhtar Donetsk | 0:1 (0:1) | ||
| 2nd (2nd leg) | Shakhtar Donetsk | - | AS Monaco | 2:2 (0:2, 1:2) aet | ||
| 1st(1st leg): 17/08/2021 20:00 | 2nd (2nd leg): 25/08/2021 20:00 | Winner: Shakhtar Donetsk | ||||
| 1st(1st leg) | BSC Young Boys | - | Ferencvárosi TC | 3:2 (2:1) | ||
| 2nd (2nd leg) | Ferencvárosi TC | - | BSC Young Boys | 2:3 (2:1) | ||
| 1st(1st leg): 18/08/2021 20:00 | 2nd (2nd leg): 24/08/2021 20:00 | Winner: BSC Young Boys | ||||
| 1st(1st leg) | Malmö FF | - | PFC Ludogorets Razgrad | 2:0 (1:0) | ||
| 2nd (2nd leg) | PFC Ludogorets Razgrad | - | Malmö FF | 2:1 (1:1) | ||
| 1st(1st leg): 18/08/2021 20:00 | 2nd (2nd leg): 24/08/2021 20:00 | Winner: Malmö FF | ||||
| 1st(1st leg) | SL Benfica | - | PSV Eindhoven | 2:1 (2:0) | ||
| 2nd (2nd leg) | PSV Eindhoven | - | SL Benfica | 0:0 (0:0) | ||
| 1st(1st leg): 18/08/2021 20:00 | 2nd (2nd leg): 24/08/2021 20:00 | Winner: SL Benfica | ||||
