Crosby, who registered an assist in last night's 8-1 victory over the Tampa Bay Lightning, is out due to an upper body injury.
Forward Matt Cooke is missing the game for undisclosed reasons.
Crosby's scratch means Evgeni Malkin will get the bulk of the workload in tonight's game.
With the secondary scoring from last night's matchup versus Tampa Bay, the Penguins look to continue their roll and will rely on players such as Chris Conner, Tyler Kennedy and Mark Letestu.
Also, Brent Johnson will start, as Marc-Andre Fleury receives a day off from his starting goaltender duties.
The Penguins will dress the same six defenseman as last night, as well as Deryk Engelland. With no healthy forwards called up to replace both Crosby and Cooke, look for Aaron Asham to play as well.
The Penguins hope to continue their momentum from last night's 8-1 victory over the Tampa Bay Lightning and stay atop the NHL's top point totals.