The Champions League finalists, who routed Athletic Bilbao 4-1 to lift the King's Cup on Wednesday, have an eight-point lead with three matches left and also hold the head-to-head advantage over their arch-rivals.
"We are taking it one step at a time and on Sunday we'll be looking for the second title," Barca defender Gerard Pique said after their cup final victory.
They are now just four goals short of the record 107 scored in a season by John Toshack's Real Madrid in the 1989/90 campaign.
With first and second all but decided, attention switches to the race for the two remaining slots for Europe's elite competition and the relegation battle.
One of the weekend's most intriguing matches sees fourth-placed Valencia (59) visit the Calderon on Sunday (1900) to play fifth-placed Atletico Madrid (58).
The Uruguay striker has scored 27 goals this season, one fewer than the league's top scorer Samuel Eto'o, and goes head-to-head with Valencia's leading marksman David Villa, who has 25.
Unai Emery's visitors were rampant in beating Real 3-0 last weekend but have been hit by suspensions to captain Carlos Marchena and midfielder David Silva.
