According to the official website of the Brazilian São Paulo Club, after the team's former coach Zuberdia left office due to poor record, they have signed with Argentina's national team legend Crespo, asking him to return to coach São Paulo again, and the two sides will sign until the end of next year.

From February to October 2021, Crespo coached Sao Paulo and led the team to win the St. Paul state championship that season, ending the club's championship drought since winning the South American Liberators Cup in 2012. During this period, Crespo led Sao Paulo to play 53 games, achieving a record of 24 wins, 19 draws and 10 losses.

After Crespo left São Paulo last time, he coached in Alduheil, Qatar and Al Ain, UAE (won the AFC Champions League during this period).