It is now three years since Real last won the league and while they carry a three-point lead over their Catalan rivals with a game in hand, they know that the Clasicos can play a key role in the destination of the championship.
While Barca have stuttered away from home this season, Real have been relentless and will be now looking for their 16th consecutive victory in all competitions, while in the league they have scored 49 goals in 14 games.
Still, the statistics go out of the window when the visitors are the domestic and European champions and have already beaten Real this season in the Spanish Super Cup.
Barcelona have generally come out on top in direct clashes between the arch rivals since the arrival of Guardiola as coach in 2008, with the notable defeat coming in the Copa del Rey final last season.
Guardiola has registered two wins and a draw at the Bernabeu when the two teams have met in the league, while including matches at Camp Nou, Barca have had five wins and a draw.
Along with this, Barcelona also knocked Real out of the Champions League in the semi-finals last spring.
Barca midfielder Xavi has tried to play down the importance of the game, however, by claiming that it will not be decisive in who wins the title.
"Madrid look the most dangerous that they have been over the last three or four years but nothing will be definite after the game," he said.
"These matches are not directly related to the final positioning in the table but it would be an important step for us if we could beat them there.
"I would like it to be an open game, where you see the potential of the two sides, but this is not down to me.
"Last season I was critical of Madrid but I think maybe this time, based on how the Super Cup went, that they will try take us on and pressure us in attack."
The game will overshadow the other top-flight action this weekend, even though Valencia will only be a point behind Barcelona if they win their match at Real Betis earlier on Saturday.
Below them, Sevilla can pinch fourth place if they beat a Levante side on a downward spiral of just one win in five games.
Malaga are still on target for a place in Europe despite their inconsistency, which saw them lose to Real Sociedad last weekend, and now they are at home to Osasuna.
Atletico Madrid are another side that cannot put a good run together and they face Espanyol, who boast a strong home record despite losing their last match on their own turf against Osasuna.
Athletic Bilbao will be hoping to bounce back after picking up just one point from two games when they play Racing Santander at San Mames.
At the other end of the table, rock bottom Real Zaragoza play host to Real Mallorca, while above them, Sporting Gijon travel to Rayo Vallecano.
Levante v Sevilla (1700GMT), Real Betis v Valencia (1900GMT), Real Madrid v Barcelona (2100GMT)
Sunday(1500GMT unless otherwise stated):
Rayo Vallecano v Sporting Gijon (1100GMT), Getafe v Granada, Villarreal v Real Sociedad, Real Zaragoza v Real Mallorca (1700GMT), Malaga v Osasuna (1700GMT), Athletic Bilbao v Racing Santander (1845GMT), Espanyol v Atletico Madrid (2030GMT)
(For more sports news update, follow Ahram Online, sports section account on twitter: @AO_Sports)