Six-time Brazilian Serie A champions Sao Paulo on Monday announced the departure of coach Muricy Ramalho.
The decision followed a 2-0 loss to Botafogo-SP on Sunday, the club's third defeat in a week, reported Xinhua.
It also comes as the 59-year-old battles ongoing health problems ahead of an undisclosed operation next week.
"I need a break to look after my health and it's time that Sao Paulo doesn't have at the moment," Ramalho said in a statement.
"I'm not saying goodbye, just see you soon. I wish everybody the best of luck."
Ramalho has suffered numerous health concerns in recent years, including kidney problems, an irregular heartbeat and a digestive disorder.
Apart from their unconvincing form in the Paulista championship, the Tricolor have struggled in the Copa Libertadores.
They need to win each of their last two group matches to progress to the knockout phase of South America's top club competition.
"I'd still have Muricy as my coach but I can't be so unfair as to put those wishes ahead of his health," Carlos Miguel Aidar, the club's president said.
"The most important thing is that he gets treated, looks after his health, and rests."
Assistant coach Milton Cruz will take charge of the club on an interim basis, Aidar added.
