The top two in LaLiga will put their title race to the side as they look to secure themselves a place in the final.
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Los Blancos beat rivals Atletico Madrid in the last eight to set up the clash with Xavi's side, who knocked out Real Sociedad to progress.
Real Madrid have won 19 Copa del Reys in total but they haven't lifted the trophy since 2014 and Carlo Ancelotti will be aiming to end that barren spell.
As for Barcelona, they are the record holders of the competition, winning this title 31 times in their history.
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Real Madrid vs Barcelona: How to follow
This Copa del Rey semi-final first leg clash will take place on Thursday, March 2.
Kick-off at the Bernabeu is scheduled for 8pm.
The match will be broadcast live on BT Sport 1 with coverage beginning at 7:45pm.
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talkSPORT will have updates throughout the evening while talkSPORT.com will also be on hand for all the best reaction as well.
To tune in to talkSPORT or talkSPORT 2 through the website, click HERE for the live stream.
You can also listen via the talkSPORT app, on DAB digital radio, through your smart speaker and on 1089 or 1053 AM.
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Real Madrid vs Barcelona: Team news
David Alaba was substituted in Real Madrid's Champions League game against Liverpool and will be absent on Thursday.
He will be joined by Rodrygo and Ferland Mendy as well as Luka Modric who is suspended.
Barcelona will be without Robert Lewandowksi for this huge clash after he picked up a hamstring injury against Almeria last time out.
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Xavi will also be missing Ousmane Dembele and Pedri, with injuries affecting some key players ahead of the game.
Although, the Catalans have been boosted by the return of Ansu Fati who should be fit to start in attack.
Real Madrid vs Barcelona: What has been said?
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When asked which team are the favourites for this El Clasico, Barcelona boss Xavi said: "We are playing for a title, Madrid are still the favourites because they are the champions of La Liga and the Champions League.
"They are a very difficult opponent and they are in a good moment. Madrid are favourites.
"My argument is that Madrid have won the last few titles and we are in the process of building: we have won one title and against them, playing extraordinary football.
"But it's Madrid, they are competing, they beat Liverpool and we have to be honest."
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He continued: "They are a very tough opponent, they don't dominate in many moments but they have those mini phases where they dominate you and in a transition, they get in your goal.
"They are a very difficult opponent on their home pitch."