Matthews missed the team's last two games with a wrist injury, an ailment he's played through for most of the campaign. He appeared to aggravate the issue last week against the Calgary Flames while crashing into the boards. The 23-year-old still leads the NHL with 18 goals.
Andersen hasn't played since Feb. 20 against the Montreal Canadiens due to a lower-body injury. Michael Hutchinson and Jack Campbell held down the fort, going 3-1-0 with only four goals against. Andersen owns a .905 save percentage and a 2.69 goals-against average over 16 games this season.
Here is Toronto's lineup with Alexander Barabanov coming out for Matthews.
Keefe also added that Campbell, who missed Monday's game after aggravating a leg injury that held him out of action for over a month, could back up Andersen on Wednesday. If he can't play, Hutchinson will dress.