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Madrid lead the standings with 38 points - four better than Barcelona, who welcome their bitter rival to the Camp Nou on Sunday in the 155th league meeting between Spain's two biggest clubs.
Madrid lead the overall series by 66-58, but both teams feel good about improving their side of the statistic.
"I find myself feeling more confident for this classic than for many others in the past," Barcelona president Joan Laporta said. "I'm convinced we are going to win."
Madrid president Ramon Calderon went as far as calling the result, saying the Spanish champions would get a 3-1 victory.
Spanish prime minister Jose Luis Rodriguez Zapatero went the other way, predicting a 3-1 win for Barcelona, according to newspaper El Mundo Deportivo.
Madrid are unbeaten in their last seven games in all competitions, while Barcelona have not lost in five, and both teams won their Champions League groups.
However, Madrid are helped by the absence of Barcelona winger Lionel Messi.
The 20-year-old Argentina international scored a hat-trick the last time the two clubs met - a 3-3 draw at the Camp Nou in March - and leads the Catalan club with eight goals.
At least striker Samuel Eto'o has returned to demonstrate his importance to coach Frank Rijkaard's attack, the Cameroon striker netting three goals in his last two games after missing more than three months with a serious thigh injury.
Eto'o, who once donned the whites of Madrid, has scored seven goals against his former club, including three since leaving Mallorca.
Advantage thanks to the ambiance
"He's a fundamental player for them and he is helping them recuperate a lot of the values of their game which they had not taken care of lately," Madrid striker Raul Gonzalez said. "But it's a very open game. In theory, the team that plays at home always has an advantage thanks to the ambiance created there, but last year we showed in 90 minutes that we deserved the victory. I think they will remember that game."
Messi's injury-time goal denied Madrid only their second win in 20 years at the Camp Nou, where Barcelona have won all 11 games this season.
Thierry Henry's return for Barcelona after a two-week layoff from injury could pose the latest setback to Ronaldinho's playing time. The Brazil playmaker has come off the bench in three of the club's last five games and was an unused substitute for the first time in a 3-0 win at Valencia on Sunday.
"It's hard to imagine a game like this one without Ronaldinho," teammate Eidur Gudjohnsen said. "If he comes in, I think you'll see him more motivated than ever."
Madrid have a full roster after defenders Christoph Metzelder and Gabriel Heinze returned for the 1-1 league cup draw against Alicante on Wednesday, but coach Bernd Schuster is unlikely to alter his starting lineup much.
Regardless of the result, Madrid will hold on to the top spot heading into the two-week Christmas break, before the league resumes on the weekend of Jan 6-7.
Atletico Madrid and Villarreal are in joint third place with 31 points. On Sunday, Atletico host Espanyol, who are unbeaten in its last 12 to sit fifth with 30 points, and Villarreal host Recreativo Huelva.
In Sunday's other matches, it's: Valladolid v Real Betis; Levante v Deportivo La Coruna; Osasuna v Mallorca; and Athletic Bilbao v Murcia.
On Saturday, Valencia play Zaragoza, Almeria face Getafe and Sevilla play sixth-placed Racing Santander.
