The veteran Maple Leafs centre is expected to miss at least three months with a fractured tibia at the base of his right knee, general manager John Ferguson said Saturday.
"He's going to need surgery to correct it," Ferguson told Leafs TV before Toronto's home game against Washington.
"We're looking at three to four months recovery."
Peca collided with Chicago Blackhawks defenceman Jim Vandermeer in the first period of Toronto's 3-1 loss to Chicago Friday night.
He had to be helped off the ice and left the dressing room on crutches, wearing an air cast.
Vandermeer received a major penalty for kneeing and a game misconduct.
"He's in quite a bit of pain," Toronto coach Paul Maurice said of Peca after the game. "We're not going to know until the doctors get a better look inside.
"This is not day-to-day. It's a bad injury."
Peca has four goals and 11 assists in 35 games this season and had been one of the team's top penalty killers.
He signed a US$2.5-million, one-year deal with the Leafs in the off-season after helping the Edmonton Oilers reach the Stanley Cup final.
The 32-year-old has 164 goals and 245 assists in 728 career games. He has twice won the Frank J. Selke Trophy for the NHL's best defensive forward.