Pato is involved in negotiations for a move to world club champions Corinthians and Robinho has also been the subject of speculation over a return home with his former club Santos among the contenders.
"I hope that only one of them leaves," Berlusconi told Radio Lombardia. "I'm especially sorry about Pato because until he started this incredible sequence of injuries, he was Milan's number one player for the future, a true champion."
Pato, signed as a 17-year-old and now 23, has suffered an extraordinary 16 muscular injuries in the last two years, costing him, among other things, a place in Brazil's squad at the 2010 World Cup.
Brazilian media have reported that he has agreed terms to join Corinthians in a deal that is expected to be finalised on Thursday.
Robinho, 28, has played for Real Madrid, Manchester City and Milan since leaving Santos in 2005, although there is a general feeling in Brazil he has never quite lived up to his early potential.
Berlusconi added that it could be two or three seasons before Milan are in the fight for honours again after they sold several top players including Sweden striker Zlatan Ibrahimovic to cut costs.
"We must devote ourselves to a work of rebuilding and I believe will not be less than three years before we get to the point where we have a team champions and turn ourselves into contenders again," he said.
Milan, reportedly among the clubs hoping to sign Ivory Coast striker Didier Drogba, are seventh in Serie A and have reached the last 16 of the Champions League.