Schedule
| Date | Dead line | Home | Away | Group | Result | Points rule |
|---|---|---|---|---|---|---|
| 09/12/21 17:45 | 09/12/21 17:45 | Alashkert Erewan | Maccabi Tel Aviv | Group A | 1-1 | 2 - 4 points |
| 09/12/21 17:45 | 09/12/21 17:45 | Linzer ASK | HJK Helsinki | Group A | 3-0 | 2 - 4 points |
| 09/12/21 17:45 | 09/12/21 17:45 | KAA Gent | Flora Tallinn | Group B | 1-0 | 2 - 4 points |
| 09/12/21 17:45 | 09/12/21 17:45 | Partizan Belgrad | Anorthosis Famagusta | Group B | 1-1 | 2 - 4 points |
| 09/12/21 17:45 | 09/12/21 17:45 | FC Zorya Lugansk | FK Bodö/Glimt | Group C | 1-1 | 2 - 4 points |
| 09/12/21 17:45 | 09/12/21 17:45 | ZSKA Sofia | AS Roma | Group C | 2-3 | 2 - 4 points |
| 09/12/21 17:45 | 09/12/21 17:45 | CFR Cluj | Jablonec | Group D | 2-0 | 2 - 4 points |
| 09/12/21 17:45 | 09/12/21 17:45 | AZ Alkmaar | Randers | Group D | 1-0 | 2 - 4 points |
| 09/12/21 20:00 | 09/12/21 20:00 | Feyenoord Rotterdam | Maccabi Haifa | Group E | 2-1 | 2 - 4 points |
| 09/12/21 20:00 | 09/12/21 20:00 | 1. FC Union Berlin | Slavia Prag | Group E | 1-1 | 2 - 4 points |
| 09/12/21 20:00 | 09/12/21 20:00 | PAOK Saloniki | Lincoln Red Imps FC | Group F | 2-0 | 2 - 4 points |
| 09/12/21 20:00 | 09/12/21 20:00 | FC Copenhagen | SK Slovan Bratislava | Group F | 2-0 | 2 - 4 points |
| 09/12/21 20:00 | 09/12/21 20:00 | Tottenham Hotspur | Stade Rennes | Group G | 0-3 | 2 - 4 points |
| 09/12/21 20:00 | 09/12/21 20:00 | Vitesse Arnheim | NS Mura | Group G | 3-1 | 2 - 4 points |
| 09/12/21 20:00 | 09/12/21 20:00 | FC Basel | Qarabag | Group H | 3-0 | 2 - 4 points |
| 09/12/21 20:00 | 09/12/21 20:00 | Omonia Nicosia | Qairat Almaty | Group H | 0-0 | 2 - 4 points |