Karlsson, who revealed after the first round that he has hairline fractures in his left foot, left Game 5 of the Eastern Conference finals in the second period Sunday after his left ankle twisted awkwardly when he collided with Penguins forward Scott Wilson along the boards.
The Penguins lead the series 3-2.
"Obviously there's a lot more at stake," Karlsson said on the morning of Game 6. "We know what can happen but we're not going to focus on that or we're not going to think about the what-ifs. We're going to do everything we can to play the game we want."
Brassard was injured during a collision with Penguins forward Chris Kunitz that kept him face down on the ice for several moments in Game 5. Ceci has battled injuries down the stretch this season.
Senators coach Guy Boucher said after the game that he was just resting his players in a blowout and they would have played if it was close.
Boucher said Tuesday that he still has a series of game-time decisions that may include playing seven defensemen, but he also ruled out two of his injured players -- defenseman Mark Borowiecki (lower body) and forward Alex Burrows (lower body) -- for Game 6.
Information from ESPN's Craig Custance was used in this report.