An injury-time Sergio Ramos equaliser ensured Madrid left Camp Nou with a share of the spoils when the sides met earlier this season, and with Los Blancos now three points ahead with a game in hand, victory would leave Barca trailing by the same margin with only five to play.
Another triumph by Barcelona at the Bernabeu would leave the teams tied on points but with Barca top on the head-to-head tiebreaker with five games left.
Barcelona face off against Real Madrid on Sunday in the biggest, most fiercely contested derby game in world football and to get in the mood Twitter has released a number of "El Clasico" themed emojis.
The news will come as a blow for Luis Enrique in the wake of his side's Champions League elimination at the hands of Juventus on Wednesday. They preserved their slender lead in the remaining games to defend the title.
Real Madrid youngster Marcos Llorente says he could never bring himself to play for Barcelona - but he isn't keen to sit on the Bernabeu bench either. "In the last few years we have been achieving good results there".
Gareth Bale has missed Madrid's last two matches after picking up a calf injury in the first-leg Champions League match against Bayern Munich.
Neymar was handed the punishment for sarcastically applauding the fourth official after being shown a second yellow card in the 2-0 loss at Malaga earlier this month.
"We have a lot of confidence and we have a very strong team". We need to understand the situation and push on.