Sabres coach Dan Bylsma said O'Reilly will miss the game with a lower-body injury he sustained during Buffalo's 4-0 win against the Columbus Blue Jackets on Friday.
O'Reilly was a 2016 NHL All-Star, has 17 goals and 49 points in 59 games this season and leads all Sabres forwards in average time on ice with 21:51 per game.
"You're taking out a guy who plays 20-plus minutes in every situation," Bylsma said. "He's the first over the boards in everything we need and that's a big part of our lineup."
Sam Reinhart will take O'Reilly's place at center.
The Sabres recalled forward Justin Bailey from Rochester of the American Hockey League to take O'Reilly's place in the lineup. Bailey made his NHL debut against the Philadelphia Flyers on Feb. 11. He's played in four games and has no points.
"Just really the size and the speed that he brought was real evident in our game bringing that speed," Bylsma said. "Again, I'll keep talking about the Philly game and there was more of it in the other games he played, but his speed and his presence in the offensive zone and at the net is something we want to continue to see from the kid."
The Sabres will also be without defenseman Cody Franson, who was injured against the Blue Jackets. Mike Weber will take his place in the lineup. Goalie Robin Lehner will start for Buffalo.
The Penguins recalled goalie Matt Murray from Wilkes-Barre/Scranton of the AHL on Sunday and he will back up starting goalie Marc-Andre Fleury against the Sabres.
"Marc's going to play," Penguins coach Mike Sullivan said. "Matt's going to back up. Marc is going to play; Matt's going to back-up… I made a decision for today."
Murray is playing in place of goalie Jeff Zatkoff, who allowed four goals in 20 shots in a 4-2 loss to the Tampa Bay Lightning on Saturday. Zatkoff started because Fleury was out sick.
Defenseman David Warsofsky was sent to Wilkes-Barre/Scranton on a long-term injury conditioning assignment to make room for Murray on the roster. Warsofsky has been out since Jan. 17 with a concussion.
The Penguins will also be without defenseman Ben Lovejoy, who was injured after he blocked a shot by Lightning forward Steven Stamkos on Saturday. Ian Cole will take Lovejoy's place.
"It's a lefty on the right side so that's probably the biggest difference because of the left-handed shot on the right side," Sullivan said. "But [Cole] has played that position in the past. He's played the right side; he did it in St. Louis a fair amount so I know he has a comfort level there, but that's probably going to be one of the biggest differences."
Here are the projected lineups:
PENGUINS
Chris Kunitz - Sidney Crosby - Phil Kessel
Carl Hagelin - Matt Cullen - Patric Hornqvist
Tom Kuhnhackl - Oskar Sundqvist - Bryan Rust
Scott Wilson - Kevin Porter - Conor Sheary
Olli Maatta - Kris Letang
Brian Dumoulin - Trevor Daley
Derrick Pouliot - Ian Cole
Marc-Andre Fleury
Matt Murray
Injured: Ben Lovejoy (lower body), Evgeni Malkin (lower body), Beau Bennett (upper body), Nick Bonino (hand), Eric Fehr (lower body), Pascal Dupuis (blood clot)
Scratched: Jeff Zatkoff, Sergei Plotnikov
SABRES
Evander Kane - Sam Reinhart - Matt Moulson
Zemgus Girgensons - Jack Eichel - Jamie McGinn
Marcus Foligno - Johan Larsson - Brian Gionta
Nicolas Deslauriers - David Legwand - Justin Bailey
Josh Gorges - Rasmus Ristolainen
Jake McCabe - Zach Bogosian
Mike Weber - Mark Pysyk
Robin Lehner
Chad Johnson
Injured: Ryan O'Reilly (lower body), Cody Franson (upper body), Tyler Ennis (upper body), Cody McCormick (blood clot)
Scratched: Carlo Colaiacovo
Status report: With the 12:30 p.m. ET start, there was no morning skate and lines are yet to be determined.
Who's hot: Eichel has 27 points in his past 27 games, and has a four-game point streak with a goal and four assists during that span. Girgensons has a two-game assist streak. … Wilson has scored a goal in two straight games. Letang has a two-game assist streak.
