Rogerio Ceni, the world's top scoring goalkeeper, broke his left ankle in practice Monday and will be sidelined for about four months.
The Sao Paulo goalkeeper will need surgery and will miss the rest of the Copa Libertadores, in addition to the final stage of the Sao Paulo state championship and part of the upcoming Brazilian league.
The injury happened after Ceni fell awkwardly during Sao Paulo's practice ahead of its match against Independiente de Medellin in Colombia on Wednesday.
Ceni had already sustained two muscle injuries this season.
The 36-year-old Ceni, a free kick and penalty kick specialist, has scored 83 goals in his 18-year career, more than any other goalkeeper.
He had been heavily criticized recently after making mistakes in the past three matches for Sao Paulo, where he has played his entire career.
He was a member of Brazil's national team which won the 1997 Confederations Cup and the 2002 World Cup. He also participated in the 2006 World Cup in Germany.
Sao Paulo is in the semifinals of the Sao Paulo state championship and leads Group 4 of the Copa Libertadores, Latin America's most important competition.