Sao Paulo replaced coach Paulo Autuori with Muricy Ramalho.
Autuori was sacked after just 17 matches in-charge Monday following Sao Paulo's 0-2 loss to Curitiba the day before, reports Xinhua.
"Sao Paulo wishes to thank Paulo Autuori for the excellent work he and his team has carried out," the club said in a statement.
Muricy, who was sacked by rivals Santos in June, returns to the club he led to three successive Campeonato Brasileiro titles from 2006-2008. His first match in-charge will be at home against Ponte Preta Thursday.
The six time league winners, who have never been relegated from Brazil's top flight, are currently third last with just 18 points from 19 matches. The bottom four clubs will drop to Brazil's Serie B next season.