Defeat at the Nou Camp for Jose Mourinho's side, who are chasing a second consecutive title after ending Barca's three-year run as champions, would stretch the Catalan club's lead over their bitter rivals to 11 points.
While that may seem insignificant compared with the 93 points that will still be available, it is worth noting Barca only dropped 15 and 18 points respectively during the whole of their title-winning campaigns in 2009-10 and 2010-11.
While nobody is writing off Real's chances of reigniting the championship race, they have been less than impressive in domestic competition, crashing to shock defeats at Getafe and Sevilla and producing a limp draw at home to Valencia.
"We are playing better with each game," playmaker Cesc Fabregas told reporters after Tuesday's 2-0 Champions League win at Benfica.
Barcelona coach Tito Vilanova, in his first season in charge, has already tasted defeat against Real when they won August's two-legged Spanish Super Cup on away goals after the tie finished 4-4 on aggregate.
His hat-trick in Wednesday's 4-1 Champions League victory at Ajax Amsterdam took his tally to 12 goals in all competitions, two more than World Player of the Year Lionel Messi of Barcelona.
It was the Portuguese forward's second treble in four days after he scored three in Sunday's 5-1 La Liga win at home to promoted Deportivo Coruna while Messi has not found the net in three matches, a worrying drought by his high standards.
Sunday's game - the 222nd meeting between the sides in official competition - takes on added significance given the latest rumblings in Catalonia over the region's desire for independence from Spain.
Real have a slight edge in the 'Clasicos' having won 88 to Barca's 87, with 46 draws.
