The Blues are currently top of their Women's Champions League group, while third-placed Real Madrid are level with Paris Saint-Germain on four points.
Match preview
After beating Sturm Graz, Manchester City and Rosenborg in the qualifying rounds, Real Madrid began the group stage with a 2-0 victory over Vllaznia.
They followed that result with a hard-fought goalless draw against PSG, before they lost away to Chelsea in November.
The Chelsea defeat leaves Real Madrid behind PSG on goal difference, while they are five points adrift of Emma Hayes's side ahead of the midweek contest.
Alberto Toril's side have returned to winning ways in their last two games, beating Alhama 5-1 before recording a comfortable 4-1 victory over Levante Las Planas at the weekend.
Although they face a tough test against the English champions on Thursday, they will be confident that they can at least pick up a point after losing just one of their last eight home games in all competitions.
Meanwhile, Chelsea are on the verge of reaching the knockout rounds after picking up maximum points from their three group games.
After beginning the competition with a narrow 1-0 away win over PSG, the Blues eased to a memorable 8-0 victory over Vllaznia.
Another positive result followed on matchday three as goals from Sophie Ingle and Erin Cuthbert guided Chelsea to a 2-0 victory against Real Madrid.
The Blues know that if they can claim all three points on Thursday then they will secure their place in the quarter-finals.
After thrashing Leicester City 8-0 at the weekend to record an 11th consecutive victory in all competitions, Chelsea will certainly be confident that they can progress to the knockout stages with two games to spare.
Real Madrid Femenino Women's Champions League form:
Real Madrid Femenino form (all competitions):
Chelsea Women Women's Champions League form:
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Chelsea Women form (all competitions):
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Team News
The hosts could be without the services of Claudia Florentino after the 24-year-old missed Saturday's victory over Levante Las Planas.
After being rested at the weekend, Kenti Robles and Ivana Andres are expected to return to the back four for Thursday's Champions League match.
Esther Gonzalez will try to add to the 12 goals she has scored in all competitions this season when she leads the line against Chelsea.
As for the visitors, they are unable to call upon Pernille Harder, who is out for an extended period after undergoing hamstring surgery.
Lauren James and Cuthbert were left on the bench for the commanding victory over Leicester, but the pair could be brought into the starting XI for the meeting with Real Madrid.
After scoring a goal and providing four assists at the weekend, Guro Reiten will retain her place in the Chelsea lineup.
Real Madrid Femenino possible starting lineup:
Misa; Robles, Kathellen, Ivana, Carmona; Zornoza, Abelleira, Weir; Del Castillo, Feller, Gonzalez
Chelsea Women possible starting lineup:
Berger; Buchanan, Bright, Eriksson; Perisset, Ingle, Cuthbert, Reiten; James, Kirby, Kerr