Sao Paulo must beat ninth-placed Goias away and need their three closest rivals, including second-placed Flamengo who visit Corinthians, to slip up in order to win another title.
Sao Paulo have 62 points, Flamengo 61, with Internacional and Palmeiras both on 59.
Inter face already relegated Sport Recife while Palmeiras meet fifth-placed Atletico Mineiro.
The clash between Brazil's two most popular clubs, Flamengo and Corinthians, brings Brazilian strikers Adriano and Ronaldo face to face.
Ronaldo will have an extra challenge, facing the club he has supported since he was a child and where he spent a good part of his recovery from knee surgery last year before opting to sign for Corinthians.
"I wouldn't want to be in his place," Adriano, also a Flamengo fan, told reporters on Thursday.
"Ronaldo always said he is a Flamengo (fan) and he went to play for Corinthians because he thought that was the best for him. It's tough to play against your club."
Should Flamengo lose, Sao Paulo, who sacked their triple championship-winning coach Muricy Ramalho and replaced him with former Brazil captain Ricardo Gomes after a poor start to the season, could extend their record of national titles to seven.
Despite their chances of winning the title early, caution has been the word at Sao Paulo in the build-up to the season's penultimate weekend.
"I think the chances are small, our direct rivals are not going to go cheaply. This race will go to the wire," said Ricardo, who carved out a coaching career in France and is seeking recognition of his coaching talents in his own country.
The fight against relegation is just as intense with Fluminense, in the drop zone for most of the season and two points from safety after five consecutive victories, hosting Vitoria.
Nautico and Santo Andre, both four points worse off than Fluminense, must win their two remaining matches to have any chance of staying in the top flight, though they meet at Santo Andre on Sunday.
