Zinedine Zidane's side - currently fourth in La Liga - have lost their last two matches to Alaves and Shakhtar Donetsk, while fifth-placed Sevilla will also enter the game off the back of a disappointing result, having suffered a 4-0 defeat to Chelsea in the Champions League.
Sevilla had been in excellent form ahead of Wednesday's Champions League clash with Chelsea, recording five straight wins in all competitions, with the run seeing them rise up the La Liga table and book their spot in the knockout round of the European Cup.
The Europa League winners have won their last three in the league, though, and appear to have recovered from a disappointing run which saw them lose three straight matches between October 17 and October 31.
Five wins, one draw and three defeats - that is how Sevilla have performed in the league this season, picking up 16 points to occupy fifth position, one point behind Madrid with a game in hand.
The hosts will be aiming to pile more misery on Los Blancos, but they have lost each of their last three La Liga games with the capital giants, including a 1-0 defeat in the corresponding match in 2019-20.
Zidane is certainly under pressure at the Bernabeu, with back-to-back losses to Alaves and Shakhtar in the league and Champions League respectively leading to more questions on the Frenchman's future.
Los Blancos are in serious danger of missing out on a spot in the knockout round of the European Cup, while they have picked up just one point from their last three matches in Spain's top flight.
Worryingly, the reigning champions have been beaten in three of their last six in La Liga, suffering defeats to Valencia and Alaves in two of their last three, which has seen them drop off the pace.
Madrid's position in the table is not catastrophic as they are only seven points off leaders Real Sociedad with a game in hand, but they trail second-placed Atletico Madrid by six points and have played one match more than Diego Simeone's side, who are regarded by many as this season's favourites.
The Whites will be eyeing their sixth league victory of the campaign on Saturday, and there is simply no downplaying the importance of the contest when it comes to Zidane's future.
Sevilla La Liga form: LLLWWW
Sevilla form (all competitions): WWWWWL
Real Madrid La Liga form: LWWLDL
Real Madrid form (all competitions): WLDWLL
Sevilla boss Lopetegui rang the changes for the clash with Chelsea, but there will be a more familiar look to the home side's XI on Saturday, with potentially only four players retaining their spots.
As for Madrid, Eden Hazard and Federico Valverde are definitely out of the contest, while neither Dani Carvajal nor Sergio Ramos is expected to be involved despite both recently stepping up their injury recoveries.
Sevilla possible starting lineup:
Vaclik; Navas, Kounde, Carlos, Rekik; Jordan, Fernando, Rakitic; Ocampos, De Jong, El Haddadi
Real Madrid possible starting lineup:
Courtois; Vazquez, Varane, Nacho, Mendy; Modric, Casemiro, Kroos; Vinicius, Benzema, Asensio
We say: Sevilla 1-1 Real Madrid
This has all of the makings of a fascinating contest, with both teams looking to bounce back from disappointing results. A win would be huge for Madrid, but Sevilla's form, aside from the Chelsea result, has been strong, and we fancy the home side to hold the reigning champions to a low-scoring draw.