Goaltender Matt Murray, who will likely be the backup, would be active for the first time since Jan. 7. He returned home to Ontario on Jan. 17 following the death of his father, James Murray, before returning to practice Monday and being scratched against the Carolina Hurricanes on Tuesday.
DeSmith has allowed four goals with a .960 save percentage through his first three NHL starts.
The Penguins, 6-2-0 in their past eight games, will look to extend their home winning streak to five games.
Center Matt Cullen will attempt to help the Wild win their third straight game when he returns to Pittsburgh for the first time since signing with Minnesota on Aug. 16. He won the Stanley Cup twice and had 63 points (29 goals, 34 assists) in two seasons with the Penguins.
Cullen had one assist in a 2-1 win against the Penguins on Oct. 28.