The team announced Monday that the bruising winger is set to miss six weeks after suffering a broken wrist in Saturday's 5-1 victory over the Vancouver Canucks.
Simmonds, 32, scored twice in the game but took a clearing attempt off his left arm in the third period. The injury was looked at by a trainer on the bench before Simmonds headed to the locker room for more treatment.
The Toronto native, who signed a one-year, $1.5 million contract in free agency to play in his hometown with the Leafs looking to add grit and leadership, failed to register a point in the first half-dozen games of the abbreviated schedule but scored five times in his past six outings.
"He's a big loss for us," Leafs coach Sheldon Keefe said of Simmonds prior to Monday's game at Scotiabank Arena against Vancouver. "He's been playing well, not just with his play, but he brings a lot to our room in a lot of other areas. That certainly will be missed."
The club is already minus another veteran with 41-year-old Joe Thornton still recovering from a fractured rib suffered Jan. 20, while rookie Nick Robertson has been out three weeks since sustaining a knee injury. Both wingers were given four-week timetables for their return to the lineup.