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| U | FC Alashkert | - | FC Sheriff | 0:1 (0:0) | ||
| R | FC Sheriff | - | FC Alashkert | 3:1 (2:1) | ||
| U: 20.07.2021 17:00 | R: 28.07.2021 19:00 | Winnaars: FC Sheriff | ||||
| U | Lincoln Red Imps | - | CFR Cluj | 1:2 (1:0) | ||
| R | CFR Cluj | - | Lincoln Red Imps | 2:0 (1:0) | ||
| U: 20.07.2021 18:00 | R: 28.07.2021 19:30 | Winnaars: CFR Cluj | ||||
| U | Dinamo Zagreb | - | Omonia Nikosia | 2:0 (0:0) | ||
| R | Omonia Nikosia | - | Dinamo Zagreb | 0:1 (0:0) | ||
| U: 20.07.2021 20:00 | R: 27.07.2021 18:00 | Winnaars: Dinamo Zagreb | ||||
| U | Ferencvárosi TC | - | FK Žalgiris | 2:0 (2:0) | ||
| R | FK Žalgiris | - | Ferencvárosi TC | 1:3 (0:1) | ||
| U: 20.07.2021 20:00 | R: 27.07.2021 19:00 | Winnaars: Ferencvárosi TC | ||||
| U | Rapid Wien | - | Sparta Praag | 2:1 (0:1) | ||
| R | Sparta Praag | - | Rapid Wien | 2:0 (1:0) | ||
| U: 20.07.2021 20:30 | R: 28.07.2021 20:30 | Winnaars: Sparta Praag | ||||
| U | Celtic FC | - | FC Midtjylland | 1:1 (1:0) | ||
| R | FC Midtjylland | - | Celtic FC | 2:1 (0:0, 1:1) n.v. | ||
| U: 20.07.2021 20:45 | R: 28.07.2021 19:45 | Winnaars: FC Midtjylland | ||||
| U | FK Kairat | - | Rode Ster Belgrado | 2:1 (1:0) | ||
| R | Rode Ster Belgrado | - | FK Kairat | 5:0 (3:0) | ||
| U: 21.07.2021 16:00 | R: 28.07.2021 20:30 | Winnaars: Rode Ster Belgrado | ||||
| U | Malmö FF | - | HJK Helsinki | 2:1 (1:0) | ||
| R | HJK Helsinki | - | Malmö FF | 2:2 (1:1) | ||
| U: 21.07.2021 19:00 | R: 27.07.2021 18:00 | Winnaars: Malmö FF | ||||
| U | NŠ Mura | - | PFC Ludogorets Razgrad | 0:0 (0:0) | ||
| R | PFC Ludogorets Razgrad | - | NŠ Mura | 3:1 (1:0) | ||
| U: 21.07.2021 20:00 | R: 28.07.2021 20:00 | Winnaars: PFC Ludogorets Razgrad | ||||
| U | Slovan Bratislava | - | BSC Young Boys | 0:0 (0:0) | ||
| R | BSC Young Boys | - | Slovan Bratislava | 3:2 (2:0) | ||
| U: 21.07.2021 20:30 | R: 28.07.2021 20:15 | Winnaars: BSC Young Boys | ||||
| U | Legia Warschau | - | FC Flora | 2:1 (1:0) | ||
| R | FC Flora | - | Legia Warschau | 0:1 (0:0) | ||
| U: 21.07.2021 21:00 | R: 27.07.2021 18:00 | Winnaars: Legia Warschau | ||||
| U | Olympiakos | - | Neftçi PFK | 1:0 (1:0) | ||
| R | Neftçi PFK | - | Olympiakos | 0:1 (0:1) | ||
| U: 21.07.2021 21:00 | R: 28.07.2021 19:00 | Winnaars: Olympiakos | ||||
| U | PSV | - | Galatasaray | 5:1 (2:1) | ||
| R | Galatasaray | - | PSV | 1:2 (0:1) | ||
| U: 21.07.2021 21:00 | R: 28.07.2021 20:00 | Winnaars: PSV | ||||
