The Maple Leafs have scored one goal in each of their two straight regulation losses without Matthews, who injured his shoulder in 3-2 victory against the Winnipeg Jets Oct. 27.
The Maple Leafs are 5-0-0 on the road this season, joining the Nashville Predators (6-0-0) as the only NHL teams without a road loss.
The Penguins were swept in a home-and-home series (0-1-1) against the New York Islanders on Tuesday and Thursday after winning their previous four games by a combined score of 23-6.
One of those four was a 3-0 win against the Maple Leafs on Oct. 18. Pittsburgh goalie Matt Murray stopped 38 shots in his seventh NHL shutout. Frederik Andersen, who is expected to start for Toronto on Saturday, made 36 saves on 37 shots in that game.