| | FIXTURE | VENUE | GMT | LOCAL | POOL |
| | Fri, 10 December 2021 |
| | Northampton Saints v Racing 92 | Franklins Gardens | 18:00 | 20:00 | Round 1 |
| |
| | Sat, 11 December 2021 |
| | Cardiff Blues v Toulouse | Cardiff Arms Park | 11:00 | 13:00 | Round 1 |
| | Bath v Leinster | Aviva Stadium | 13:15 | 15:15 | Round 1 |
| | Bordeaux v Leicester Tigers | Stade Chaban-Delmas | 14:15 | 16:15 | Round 1 |
| | Bristol v Scarlets | Ashton Gate | 15:30 | 17:30 | Round 1 |
| | Clermont v Ulster | Stadium Marcel-Michelin | 16:30 | 18:30 | Round 1 |
| | Exeter Chiefs v Montpellier | Sandy Park Stadium | 18:00 | 20:00 | Round 1 |
| |
| | Sun, 12 December 2021 |
| | Connacht v Stade Francais | Sportsground | 11:00 | 13:00 | Round 1 |
| | Ospreys v Sale Sharks | Swansea RFC | 11:00 | 13:00 | Round 1 |
| | Munster v Wasps | Coventry Building Society Arena | 13:15 | 15:15 | Round 1 |
| | Glasgow Warriors v La Rochelle | Stade Marcel Deflandre | 14:15 | 16:15 | Round 1 |
| | Castres v Harlequins | Stade Pierre Fabre | 16:30 | 18:30 | Round 1 |
| |
| | Fri, 17 December 2021 |
| | Northampton Saints v Ulster | Kingspan Stadium | 18:00 | 20:00 | Round 2 |
| | Leinster v Montpellier | GGL Stadium | 19:00 | 21:00 | Round 2 |
| |
| | Sat, 18 December 2021 |
| | Bath v La Rochelle | Recreation Ground | 11:00 | 13:00 | Round 2 |
| | Cardiff Blues v Harlequins | Twickenham Stoop | 11:00 | 13:00 | Round 2 |
| | Clermont v Sale Sharks | AJ Bell Stadium | 13:15 | 15:15 | Round 2 |
| | Exeter Chiefs v Glasgow Warriors | Scotstoun Stadium | 15:30 | 17:30 | Round 2 |
| | Ospreys v Racing 92 | Paris La Defense Arena | 16:30 | 18:30 | Round 2 |
| | Castres v Munster | Thomond Park | 18:00 | 20:00 | Round 2 |
| |
| | Sun, 19 December 2021 |
| | Connacht v Leicester Tigers | Welford Road | 11:00 | 13:00 | Round 2 |
| | Bordeaux v Scarlets | Parc y Scarlets | 11:00 | 13:00 | Round 2 |
| | Toulouse v Wasps | Stade Ernest Wallon | 14:15 | 16:15 | Round 2 |
| | Bristol v Stade Francais | Stade Jean Bouin | 16:30 | 18:30 | Round 2 |
| |
| | Fri, 14 January 2022 |
| | Cardiff Blues v Harlequins | Cardiff Arms Park | 18:00 | 20:00 | Round 3 |
| | Castres v Munster | Stade Pierre Fabre | 19:00 | 21:00 | Round 3 |
| |
| | Sat, 15 January 2022 |
| | Toulouse v Wasps | Coventry Building Society Arena | 11:00 | 13:00 | Round 3 |
| | Connacht v Leicester Tigers | Sportsground | 13:15 | 15:15 | Round 3 |
| | Ospreys v Racing 92 | Swansea RFC | 13:15 | 15:15 | Round 3 |
| | Exeter Chiefs v Glasgow Warriors | Sandy Park Stadium | 15:30 | 17:30 | Round 3 |
| | Bath v La Rochelle | Stade Marcel Deflandre | 16:30 | 18:30 | Round 3 |
| | Bristol v Stade Francais | Ashton Gate | 18:00 | 20:00 | Round 3 |
| |
| | Sun, 16 January 2022 |
| | Leinster v Montpellier | RDS Arena | 11:00 | 13:00 | Round 3 |
| | Northampton Saints v Ulster | Franklins Gardens | 13:15 | 15:15 | Round 3 |
| | Bordeaux v Scarlets | Stade Chaban-Delmas | 14:15 | 16:15 | Round 3 |
| | Clermont v Sale Sharks | Stadium Marcel-Michelin | 16:30 | 18:30 | Round 3 |
| |
| | Fri, 21 January 2022 |
| | Castres v Harlequins | Twickenham Stoop | 18:00 | 20:00 | Round 4 |
| |
| | Sat, 22 January 2022 |
| | Bath v Leinster | Recreation Ground | 11:00 | 13:00 | Round 4 |
| | Cardiff Blues v Toulouse | Stade Ernest Wallon | 12:00 | 14:00 | Round 4 |
| | Bordeaux v Leicester Tigers | Welford Road | 13:15 | 15:15 | Round 4 |
| | Bristol v Scarlets | Parc y Scarlets | 15:30 | 17:30 | Round 4 |
| | Clermont v Ulster | Kingspan Stadium | 15:30 | 17:30 | Round 4 |
| | Glasgow Warriors v La Rochelle | Scotstoun Stadium | 18:00 | 20:00 | Round 4 |
| |
| | Sun, 23 January 2022 |
| | Ospreys v Sale Sharks | AJ Bell Stadium | 11:00 | 13:00 | Round 4 |
| | Connacht v Stade Francais | Stade Jean Bouin | 12:00 | 14:00 | Round 4 |
| | Munster v Wasps | Thomond Park | 13:15 | 15:15 | Round 4 |
| | Northampton Saints v Racing 92 | Paris La Defense Arena | 14:15 | 16:15 | Round 4 |
| | Exeter Chiefs v Montpellier | GGL Stadium | 16:30 | 18:30 | Round 4 |
