Under the tutelage of Zinedine Zidane, Real knocked out Liverpool en route to the semi-finals last term but were ultimately sent packing by eventual winners Chelsea.
Los Blancos enter their inaugural Champions League clash on the back of a stellar 5-2 success against Celta Vigo in La Liga action, with Karim Benzema scoring a hat-trick while Vinicius Junior and new arrival Eduardo Camavinga also got in on the act.
Here, Sports Mole rounds up all of Real's latest injury and suspension news ahead of the contest.
Toni Kroos
Status: Major doubt
Type of injury: Hip
Possible return date: September 15 (vs. Inter)
Toni Kroos was thought to have an outside chance of returning to the fold against Celta but did not make the cut at the weekend. The German midfielder is facing a race against time to be fit for Wednesday, although new recruit Camavinga demonstrated his worth to the side last time out.
Ferland Mendy
Status: Out
Type of injury: Leg
Possible return date: Unknown
Ferland Mendy continues to recover from the leg issue he sustained at the back end of the 2020-21 season, and the left-back is set to remain out of contention for now.
Dani Ceballos
Status: Out
Type of injury: Ankle
Possible return date: Unknown
Dani Ceballos suffered a nasty-looking ankle injury while representing Spain at the Tokyo 2020 Olympics and will not be ready to feature here, although recent reports have claimed that he is set to return to Real Betis on loan in January anyway.
Gareth Bale
Status: Out
Type of injury: Hamstring
Possible return date: Unknown
Gareth Bale was not available for the win over Celta after suffering a hamstring injury and is set for scans on Monday, meaning that he is incredibly unlikely to make the cut here.
David Alaba
Status: Major doubt
Type of injury: Muscle
Possible return date: Unknown
David Alaba was ruled out of Sunday's game due to reported muscular overload, despite returning to training a few days beforehand, and the former Bayern Munich man remains a doubt for Wednesday.
Luka Jovic
Status: Major doubt
Type of injury: Abdominal
Possible return date: Unknown
Luka Jovic was also ruled out of the weekend's win after reportedly suffering from gastroenteritis, and it remains to be seen if the striker will recover in time for Wednesday.
REAL MADRID'S SUSPENSION LIST
Real Madrid have no players suspended for this match.