The Blues registered a 1-1 draw at the Alfredo di Stefano Stadium last week, where they secured a crucial away goal.
The west London club dominated the proceedings in the first half but failed to fully capitalise on their scoring chances.
Christian Pulisic scored an early goal for the Blues. Karim Benzema levelled the scores with Los Blancos’ only shot on target.
Thomas Tuchel will be hoping for a better attacking display. The club are aiming to reach the final for the first time since 2012.
With the away-goal advantage, a goalless draw would be sufficient to ensure their place in the final in Istanbul later this month.
Edouard Mendy produced a fine performance against Fulham with three key saves. He kept his 23rd clean sheet from his 39th appearance for the club. He is expected to start in goal ahead of Kepa Arrizabalaga.
In defence, Tuchel may prefer the same line-up from the reverse fixture in Madrid. Antonio Rudiger is likely to return to the starting XI in place of Kurt Zouma. The German will wear a mask for a facial injury sustained last week.
Reece James should drop to the bench, with club captain Cesar Azpilicueta likely to feature from the right wing-back spot. Ben Chilwell will start on the opposite side ahead of Marcos Alonso. He has made the position his own in recent weeks.
Tuchel managed to give a break to both N’Golo Kante and Jorginho last weekend, with Mason Mount and Billy Gilmour playing in midfield. The experienced duo are expected to start this game. Mateo Kovacic is a major doubt with a hamstring injury.
With the pair’s return, Mount should feature in a more advanced attacking role. He is likely to take his place from Hakim Ziyech. There could be another change with Christian Pulisic returning to the line-up ahead of Timo Werner.
Tuchel has persisted with Werner in the starting line-up in recent weeks, but he could drop to the bench instead of Kai Havertz, who starred against the Cottagers with a brace. The German is likely to feature in the false number nine role.
How Chelsea could line up against Real Madrid
Stats from Transfermarkt.com