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| H | RB Salzburg | - | Brøndby IF | 2:1 (0:1) | ||
| R | Brøndby IF | - | RB Salzburg | 1:2 (0:2) | ||
| H: 17.08.2021 21:00 | R: 25.08.2021 21:00 | Sieger: RB Salzburg | ||||
| H | FC Sheriff | - | Dinamo Zagreb | 3:0 (1:0) | ||
| R | Dinamo Zagreb | - | FC Sheriff | 0:0 (0:0) | ||
| H: 17.08.2021 21:00 | R: 25.08.2021 21:00 | Sieger: FC Sheriff | ||||
| H | AS Monaco | - | Shakhtar Donetsk | 0:1 (0:1) | ||
| R | Shakhtar Donetsk | - | AS Monaco | 2:2 (0:2, 1:2) n.V. | ||
| H: 17.08.2021 21:00 | R: 25.08.2021 21:00 | Sieger: Shakhtar Donetsk | ||||
| H | BSC Young Boys | - | Ferencvárosi TC | 3:2 (2:1) | ||
| R | Ferencvárosi TC | - | BSC Young Boys | 2:3 (2:1) | ||
| H: 18.08.2021 21:00 | R: 24.08.2021 21:00 | Sieger: BSC Young Boys | ||||
| H | Malmö FF | - | PFC Ludogorets Razgrad | 2:0 (1:0) | ||
| R | PFC Ludogorets Razgrad | - | Malmö FF | 2:1 (1:1) | ||
| H: 18.08.2021 21:00 | R: 24.08.2021 21:00 | Sieger: Malmö FF | ||||
| H | SL Benfica | - | PSV Eindhoven | 2:1 (2:0) | ||
| R | PSV Eindhoven | - | SL Benfica | 0:0 (0:0) | ||
| H: 18.08.2021 21:00 | R: 24.08.2021 21:00 | Sieger: SL Benfica | ||||
