Kunitz and Orpik will sit for the second time in the past three games. They are listed as day-to-day and their ailments are not expected to be long-term issues, Penguins coach Dan Bylsma said.
Penguins forward Harry Zolnierczyk will play against his former team after being recalled Friday from the American Hockey League.
The Flyers would clinch third place in the Metropolitan Division and a date with the New York Rangers in the first round of the Stanley Cup Playoffs with a regulation or overtime victory. If they win in a shootout or lose, they will have to await the results of the final games for the Columbus Blue Jackets (Saturday night) and potentially the Detroit Red Wings (Sunday) before learning their playoff opponent.
Kunitz, who serves as the net-front presence on the Penguins' top-ranked power play, has scored a career-high 67 points and 35 goals in 77 games this season. His contributions could be missed against the Flyers, whose special teams were dominant in a weekend series against the Penguins on March 15 and 16.
Flyers forward Matt Read had two shorthanded goals, while Philadelphia scored on three of its seven power-play opportunities and shut down Pittsburgh on all nine of its chances in the two Flyers wins.
"The Flyers won on both sides of the ledger in both of those games. They won with their power play and they stymied our power play," Bylsma said. "It ended up being a big difference in both of our games, in both of our scores, and was really a catalyst in the first period. It really started the game, both in the one in Philadelphia and the one here.
"In this particular matchup, it's even maybe more important than in a regular matchup. Our penalty kill has to do a job against their power play. We know what they're good at, we know what they're trying to do."
Goalie Marc-Andre Fleury will start for Pittsburgh in its first of back-to-back games to end its regular season.
Here are the expected lineups for the Penguins and Flyers:
Injured: Chris Kunitz (undisclosed), Brooks Orpik (undisclosed), Evgeni Malkin (foot), Marcel Goc (foot), Joe Vitale (upper body), Chris Conner (broken foot), Pascal Dupuis (ACL), Tomas Vokoun (pelvis)
Injured: Niklas Grossman (ankle)
Suspended: Zac Rinaldo