Los Blancos lost 1-0 to Barcelona in the first leg of their Copa del Rey semi-final last time out, while Real Betis will enter the match off the back of a 3-2 victory at Elche in the league on February 24.
Match preview
Real Betis appear to have rediscovered their form at the perfect time, winning each of their last three matches in Spain's top flight, overcoming Almeria, Real Valladolid and Elche.
Manuel Pellegrini's side were involved in a five-goal thriller with Elche last Friday, with the Green and Whites coming from two goals behind to win 3-2, Willian Jose netting the only goal of the contest in the fifth minute of additional time at the end of the 90.
Real Betis are currently fifth in the table, two points behind fourth-placed Atletico Madrid and just three behind third-placed Real Sociedad, while they are crucially six points ahead of seventh-placed Villarreal.
Pellegrini's team will certainly be eyeing a top-four finish in La Liga this season, but they could also qualify for next season's Champions League through the Europa League.
The Green and Whites have been drawn against Manchester United in the last-16 stage of the competition, with the first leg between the two teams set to take place at Old Trafford next Thursday.
Real Betis' immediate focus will be on the league, though, as they aim to beat Real Madrid in Spain's top flight for the first time since March 2020.
Real Madrid have already overcome Real Betis this season, running out 2-1 winners at Bernabeu back in September, so they will be bidding to do the league double over the Seville outfit this weekend.
Carlo Ancelotti's side were held to a 1-1 draw by Atletico Madrid in the league last Saturday, but they are only seven points off division leaders Barcelona, who surprisingly lost 1-0 at Almeria last Sunday.
Real Madrid will know that they cannot afford many more slip-ups if they are to catch Barcelona at the summit, while the capital outfit have serious work to do in the Copa del Rey, having lost 1-0 to Xavi's side in the first leg of their semi-final at Bernabeu on Thursday night.
Los Blancos now have two league games against Real Betis and Espanyol before welcoming Liverpool for the second leg of their last-16 Champions League tie, boasting a 5-2 advantage from the first leg.
Real Madrid will then head to Camp Nou for El Clasico in La Liga, and it is likely that they will have to win that match in order to stand a serious chance of moving past the current league leaders.
The reigning champions have the second-best away record in Spain's top flight this season, but all three of their losses in the league in 2022-23 have come on their travels.
Real Betis La Liga form:
W
L
L
W
W
W
Real Madrid La Liga form:
D
W
L
W
W
D
Real Madrid form (all competitions):
W
W
W
W
D
L
Team News
Real Betis have lost Nabil Fekir for the rest of the season due to a serious knee injury, while Sergio Canales, Rui Silva, Edgar Gonzalez and Juan Cruz are also on the sidelines.
Ayoze Perez could drop into a deeper position to allow Borja Iglesias to return at centre-forward, while Juan Miranda's impressive performance off the bench against Elche could see him start at left-back.
Guido Rodriguez will return from suspension, meanwhile, to line up alongside William Carvalho in midfield.
Real Madrid will be missing experienced midfielder Luka Modric through suspension due to the booking that he picked up in the Madrid derby last weekend.
David Alaba and Ferland Mendy remain on the sidelines with hamstring problems, but Los Blancos did not suffer any fresh issues against Barcelona on Thursday night.
There could be two changes from the side that started El Clasico, with Aurelien Tchouameni and Dani Ceballos potentially coming in for Modric and Toni Kroos, but Nacho should continue at left-back.
Real Betis possible starting lineup:
Bravo; Ruibal, Pezzella, Felipe, Miranda; Carvalho, Rodriguez; Henrique, Perez, Juanmi; Iglesias
Real Madrid possible starting lineup:
Courtois; Carvajal, Militao, Rudiger, Nacho; Ceballos, Tchouameni, Camavinga; Valverde, Benzema, Vinicius
We say: Real Betis 1-2 Real Madrid
This is a very tough match for Real Madrid, and it would not be a surprise to see them drop valuable points on Sunday night. Ancelotti will have his team fired-up following the loss to Barcelona, though, and we are tipping Los Blancos to navigate their way to a huge three points in Seville.