Madrid have won 15 more points in all in La Liga under the guidance of Zinedine Zidane.
Madrid have won 15 more points in all in La Liga under the guidance of Zinedine Zidane since the sides last met in April and are riding a 31-game unbeaten run in all competitions.
"On Saturday we have more to play for than Madrid, they can lose, we can't," said Barcelona defender Gerard Pique.
Barca are off to their worst league start in nine seasons.
However, coach Luis Enrique believes much of the media criticism of his side has been overblown, citing the institutional crisis that Barca overcame in the January his debut season in 2015 to win the treble.
"We remain favourites for all the titles, but it is evident we have to improve," said Enrique.
"We lack consistency, but don't exaggerate. In my first season you (the media) exaggerated and we ended up winning the treble."
The biggest match in club football is expected to capture an audience of 650 million people worldwide, according to figures released by La Liga.
"I am not going to say it is just another game, it is a very important match, it has a special meaning....a special taste," Real president Florentino Perez told AFP.
"No one hides that is has a worldwide impact, it is seen by millions of people across the world, like the World cup final."
Yet, the composed Zidane refused to accept that a first Liga title in five years would be Madrid's to lose should they bag victory at the Camp Nou.
"I am not thinking about the consequences," he said after giving a goalscoring debut to his son Enzo in Madrid's 6-1 Copa del Rey thrashing of Cultural Leonesa on Wednesday.
"We are thinking about preparing well for the game, and, whatever happens, it will not be decisive."
Both sides are blighted by injury concerns.
Madrid will be without Gareth Bale with the Welshman now set to miss up to four months after an ankle operation, whilst Toni Kroos is also sidelined by a broken foot.
Tough tackling midfielder Casemiro made his first appearance in two months in midweek and could come into contention to partner the Croatian duo of Luka Modric and Mateo Kovacic.
Cristiano Ronaldo has shot to the top of La Liga's goalscoring charts once more with five in his last two league outings and looks set to be partnered by Karim Benzema and Lucas Vazquez in Bale's absence.
Barca are sweating on the fitness of Jordi Alba and Pique, who both struggled through the 90 minutes in a 1-1 draw at Real Sociedad described as a "miracle" by Enrique given the state of Barca's display.
However, the champions will be hugely boosted by the return of captain Andres Iniesta, whilst the front three of Lionel Messi, Luis Suarez and Neymar are all fit to start.
The clash between the top two offers Sevilla and Atletico Madrid the chance to make up ground in the title race.
Sevilla sit behind Barca only on goal difference in third and can close on Real when they visit winless Granada on Saturday lunchtime.
Atletico have bounced back from their Madrid derby humbling at the hands of Real two weeks ago with three wins and 11 goals without conceding since.
However, they will need to end a seven-game unbeaten streak in the league by Espanyol to keep that run going at the Vicente Calderon.
Fixtures (all times GMT)
Granada v Sevilla (1200), Barcelona v Real Madrid (1515), Leganes v Villarreal (1730), Atletico Madrid v Espanyol (1945)
Real Betis v Celta Vigo (1100), Athletic Bilbao v Eibar (1515), Alaves v Las Palmas, Sporting Gijon v Osasuna (1730), Valencia v Malaga (1945)
Deportivo la Coruna v Real Sociedad (1945)