Barca lead second-placed Real Madrid by 13 points with six games left to play, and could move 16 clear with a victory at struggling Athletic Bilbao.
That would be enough to deliver them the title should Real then lose at third-placed Atletico Madrid.
The Catalans, however, will travel back to the Nou Camp with their minds turning to how they might overturn a 4-0 deficit against Bayern Munich four days later.
The top two are likely to field weakened teams in anticipation of demanding European second legs next week.
Jose Mourinho's side have publicly given up on the league to focus on Europe and need to recover from a 4-1 drubbing at Borussia Dortmund.
Only a Barca win and a Real defeat can deliver coach Tito Vilanova's first league title as Madrid hold a superior head-to-head record.
Barca take on a Bilbao side lying 14th in the standings and in danger of slipping into the relegation battle, while on paper Real have a much-more demanding fixture at the Calderon.
Atletico have a chance to end almost 14 years of derby pain and to move above their distracted neighbours with a victory, and coach Diego Simeone has challenged his side to seize their opportunity.
Real are three points ahead of them and hold the edge in head-to-heads should they finish level, after a 2-0 victory at the Bernabeu earlier in the season.
CHANGE HISTORY
The Madrid derby usually induces pessimism in the red and white half of the Spanish capital with Atletico last managing to beat their city rivals with a 3-1 away win in 1999.
They have suffered nine defeats to Real in their last 10 league meetings at the Calderon, but the man who has engineered this year's impressive campaign is keen to change history.
"You have to go back many years before you find a time when we were competing for league positions as well as for the game," Argentine Simeone told a news conference on Wednesday.
"We have played them in many different circumstances and it hasn't gone well. Saturday is a new opportunity and you have to make the most of it."
The game also acts as a prelude for the King's Cup final when the two sides will clash again, this time at the Bernabeu on May 17.
Atletico were boosted when striker Diego Costa's yellow card from last weekend was overturned on appeal on Wednesday, meaning their pugnacious striker is available to play.
Atletico are close to securing a berth in the Champions League group stage, but the battle for the fourth spot, which requires entry through qualifying, is set to run to the end of the season.
Surprise-package Real Sociedad occupy fourth place, 13 points behind Atletico, but two ahead of fifth-placed Valencia who visit Sociedad's Anoeta stadium on Sunday.
