The two clubs have enjoyed a fierce rivalry throughout their illustrious histories and every year this fixture demands even greater global attention.
Little excuse is needed to hype up the biggest game in club football, but this weekend's meeting at Camp Nou carries extra significance as the season enters its final stretch.
With 11 matches remaining, Barca lead Real by one point at the summit, while reigning champions Atletico Madrid have dropped off the pace in recent weeks.
Real tasted victory in the reverse fixture back in October as goals from Cristiano Ronaldo, Pepe and Karim Benzema helped them to a 3-1 success after Neymar's early opener.
"We know that there's a lot of pressure, but that's normal because it's a huge match," Benzema told Real sponsor bwin's official website. "Every player who loves football wants to play in it.
"We're going to prepare well for the match, all together, to go to Barcelona and win. We're only thinking about working hard to win together, as always. If we defend well we can do it.
"We can repeat the result from the first half of the season. We're in good shape to win and put in a performance like the one we put in.
"We're Real Madrid. To score again like I did in our first meeting of the season, I need a bit of luck and nothing else."
As ever, much of the focus will be on each side's respective talisman, as the performances of Lionel Messi and Ronaldo continue to provoke debate over which one deserves to be considered the greatest player on the planet.
In 2014-15, Messi leads the way in the goalscoring charts - with 32 in the league and 43 in all competitions, while Ronaldo has 41 goals all told, 30 of which have come in La Liga.
Carlo Ancelotti's Real side have dropped points against both Villarreal and Athletic Bilbao in recent weeks, which allowed Barca to overtake them at the top with a run of nine wins from 10 matches.
Both sides have progressed to the last eight of the UEFA Champions League in the past fortnight, with holders Real handed a repeat of last season's final as they were drawn against Atletico, while Barca have been pitted against Ligue 1 champions Paris Saint-Germain.
Sunday's game sees world football's two most fearsome attacking trios go head to head as Messi, Neymar and Luis Suarez go up against Ronaldo, Benzema and Gareth Bale.
Gerard Pique will be charged with containing Real's attacking threat and will relish the occasion.
"This is one of the most special games of the year, because of the rivalry between us and because we're usually playing for titles against them," he told Barca's official site.
"They're another great team, with great players and that makes it so much more special. You have to prepare several days in advance, but it's always a game you're really looking forward to."
Real's only fitness concern surrounds James Rodriguez, who has not featured since fracturing a metatarsal against Sevilla in early February, while Barca expect to have Sergio Busquets back after missing the last three games with an ankle injury.
