The Blues boss has conceded that Kovacic will not return from a thigh issue in time to feature this weekend, while Rudiger is out with an injury picked up in the Champions League.
Veteran defender Cesar Azpilicueta may be spared for the visit of Los Blancos next week, meaning that Kurt Zouma could rejoin the defence alongside Andreas Christensen and Thiago Silva, with the latter unlikely to get any rest while Rudiger recuperates.
Reece James was only given a 25-minute run out in the Champions League so is likely to start here, but Ben Chilwell has played a lot of football recently and may be given the night off as Marcos Alonso hopes to impress.
Christian Pulisic could also make way for Hakim Ziyech despite his impressive opener in Madrid, while Tammy Abraham and Olivier Giroud's frustrations are likely to continue as Kai Havertz bids to lead the line.
Chelsea possible starting lineup:
Mendy; Zouma, Silva, Christensen; James, Jorginho, Kante, Alonso; Ziyech, Mount; Havertz
Watch the Sports Mole Football Shorts prediction for this game below: