Defenceman Cody Franson left with what appeared to be a left leg injury and forward David Booth suffered a bone bruise after blocking a shot in Toronto's 3-2 shootout win over Buffalo on Sunday.
Peter Holland scored the winner in the third round of the shootout for the Leafs (4-1-1), while Phil Kessel and James van Riemsdyk had goals in regulation time.
Toronto head coach Randy Carlyle didn't have a definitive answer when asked for an update on Franson.
"He went awkwardly into the boards and he fell pretty hard," said Carlyle. "It looked like he hit his knee cap or some part of the leg went underneath him into the boards first so I can't really make a comment other than that synopsis."
The Leafs lost defenceman Henrik Tallinder to a dislocated shoulder and forward David Clarkson to a facial injury in Friday's 6-4 victory in Buffalo.
"You never really like to see hits at that part of the ice when guys are skating that fast into the wall," said van Riemsdyk of the Franson play. "You'd like to see a little more caution used there. If you're going to hit a guy there, at least guide him.
"Obviously it's a fast game, I'm sure he wasn't trying to hurt him or anything, but hopefully Franny's OK."
Booth played over six minutes in the second period after blocking the shot before leaving.
The Sabres (1-2-1) also fell victim to injuries on Sunday, losing forwards Patrick Kaleta and Johan Larsson. Mikhail Grigorenko and Nicolas Deslauriers scored for Buffalo.
Jonathan Bernier made 36 saves in his first complete game while Andrey Makarov stopped 26 shots for Buffalo.
Franson went heavily into the end boards behind the Leafs net after he was shoved by Sabres forward Torrey Mitchell at 11:15 of the third. The Leafs defenceman had to be helped off while putting no pressure on his left leg.
Sunday marked the first time the Leafs top line of James van Riemsdyk, Phil Kessel and Tyler Bozak skated as a unit in the pre-season.
Kessel got Toronto on the board in the second period with his first goal of the pre-season. Van Riemsdyk tied it 2-2 midway through the third with a power-play goal, putting home the rebound off a Kessel shot.
"It was fun, we were a little off at times. We thought we could've had a lot more opportunities or goals. Their goalie played pretty well," said Bozak, who was playing in just his second pre-season game after nursing a lower body injury. "Definitely fun to be back out there playing with them and we created some good chances."
The Sabres opened the scoring 25 seconds in to the second as Grigorenko knocked down a Cody Hodgson saucer pass and beat Bernier stick-side for his first of the pre-season on Buffalo's eighth shot of the night.
Sabres head coach Ted Nolan praised Grigorenko's work ethic post-game.
"I'm a big believer that good things happen when you do the right thing more often than not," said Nolan. "He did the right thing this summer by working himself in better shape. He came to camp with a real positive attitude. Willing to earn things and he's had a tremendous attitude from the get go.
"It's great to see him get rewarded tonight."
Deslauriers gave Buffalo a 2-0 lead at 9:24 of the second getting his stick on a Rasmus Ristolainen point shot.
The Sabres lost a pair of bodies in the first when Kaleta took a Morgan Rielly slapshot to the face at 11:32 of the opening period.
Then with less than a minute remaining in the first, Larsson skated into the elbow of an unsuspecting Petter Granberg and headed for the dressing room early.
Neither player returned. Nolan said both players would be re-evaluated when the team returned to Buffalo.
Notes: Leafs forward David Clarkson is scheduled to see a specialist Monday for his cheekbone injury. … Toronto defenceman Stephan Robidas (leg) has been cleared for contact and is targeting the pre-season finale Oct. 3 for his Leafs debut. … Blue liner Henrik Tallinder is awaiting further results on his dislocated shoulder.