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| H | FC Flora | - | Hibernians FC | 2:0 (0:0) | ||
| R | Hibernians FC | - | FC Flora | 0:3 (0:2) | ||
| H: 06.07.2021 18:00 | R: 13.07.2021 18:00 | Sieger: FC Flora | ||||
| H | HJK Helsinki | - | FK Budućnost Podgorica | 3:1 (3:1) | ||
| R | FK Budućnost Podgorica | - | HJK Helsinki | 0:4 (0:3) | ||
| H: 06.07.2021 18:00 | R: 13.07.2021 20:30 | Sieger: HJK Helsinki | ||||
| H | Ferencvárosi TC | - | KF Prishtina | 3:0 (0:0) | ||
| R | KF Prishtina | - | Ferencvárosi TC | 1:3 (0:0) | ||
| H: 06.07.2021 18:00 | R: 13.07.2021 20:00 | Sieger: Ferencvárosi TC | ||||
| H | CFR Cluj | - | Borac Banja Luka | 3:1 (2:1) | ||
| R | Borac Banja Luka | - | CFR Cluj | 2:1 (0:0, 2:0, 2:1) n.V. | ||
| H: 06.07.2021 19:00 | R: 13.07.2021 20:00 | Sieger: CFR Cluj | ||||
| H | FK Žalgiris | - | Linfield FC | 3:1 (2:0) | ||
| R | Linfield FC | - | FK Žalgiris | 1:2 (0:2) | ||
| H: 06.07.2021 19:00 | R: 13.07.2021 20:45 | Sieger: FK Žalgiris | ||||
| H | CS FOLA Esch | - | Lincoln Red Imps | 2:2 (0:1) | ||
| R | Lincoln Red Imps | - | CS FOLA Esch | 5:0 (2:0) | ||
| H: 06.07.2021 19:30 | R: 13.07.2021 18:00 | Sieger: Lincoln Red Imps | ||||
| H | KF Shkëndija 79 | - | NŠ Mura | 0:1 (0:1) | ||
| R | NŠ Mura | - | KF Shkëndija 79 | 5:0 (2:0) | ||
| H: 06.07.2021 20:00 | R: 13.07.2021 20:00 | Sieger: NŠ Mura | ||||
| H | Dinamo Tbilisi | - | Neftçi PFK | 1:2 (1:1) | ||
| R | Neftçi PFK | - | Dinamo Tbilisi | 2:1 (0:0) | ||
| H: 07.07.2021 18:00 | R: 14.07.2021 19:00 | Sieger: Neftçi PFK | ||||
| H | FK Bodø/Glimt | - | Legia Warszawa | 2:3 (1:2) | ||
| R | Legia Warszawa | - | FK Bodø/Glimt | 2:0 (1:0) | ||
| H: 07.07.2021 18:00 | R: 14.07.2021 20:00 | Sieger: Legia Warszawa | ||||
| H | Slovan Bratislava | - | Shamrock Rovers | 2:0 (1:0) | ||
| R | Shamrock Rovers | - | Slovan Bratislava | 2:1 (1:0) | ||
| H: 07.07.2021 18:30 | R: 13.07.2021 21:00 | Sieger: Slovan Bratislava | ||||
| H | Dinamo Zagreb | - | Valur Reykjavík | 3:2 (2:0) | ||
| R | Valur Reykjavík | - | Dinamo Zagreb | 0:2 (0:1) | ||
| H: 07.07.2021 19:00 | R: 13.07.2021 22:00 | Sieger: Dinamo Zagreb | ||||
| H | PFC Ludogorets Razgrad | - | Shakhter Soligorsk | 1:0 (0:0) | ||
| R | Shakhter Soligorsk | - | PFC Ludogorets Razgrad | 0:1 (0:0) | ||
| H: 07.07.2021 19:00 | R: 13.07.2021 21:30 | Sieger: PFC Ludogorets Razgrad | ||||
| H | Maccabi Haifa | - | FK Kairat | 1:1 (1:0) | ||
| R | FK Kairat | - | Maccabi Haifa | 2:0 (1:0) | ||
| H: 07.07.2021 19:00 | R: 14.07.2021 16:00 | Sieger: FK Kairat | ||||
| H | Malmö FF | - | Riga FC | 1:0 (0:0) | ||
| R | Riga FC | - | Malmö FF | 1:1 (0:1) | ||
| H: 07.07.2021 19:00 | R: 13.07.2021 18:00 | Sieger: Malmö FF | ||||
| H | KF Teuta Durrës | - | FC Sheriff | 0:4 (0:2) | ||
| R | FC Sheriff | - | KF Teuta Durrës | 1:0 (1:0) | ||
| H: 07.07.2021 19:00 | R: 13.07.2021 19:00 | Sieger: FC Sheriff | ||||
| H | Connah's Quay Nomads | - | FC Alashkert | 2:2 (1:2) | ||
| R | FC Alashkert | - | Connah's Quay Nomads | 1:0 (0:0, 0:0, 1:0) n.V. | ||
| H: 07.07.2021 20:00 | R: 14.07.2021 17:00 | Sieger: FC Alashkert | ||||
