O'Reilly sustained a left shoulder injury Monday in the Avalanche's 4-3 loss to the Calgary Flames. John Mitchell will take his place on a line with Gabriel Landeskog and Paul Stastny. Rookie Nathan MacKinnon will move to left wing with Matt Duchene and Jamie McGinn.
The Avalanche also will need to shuffle the third and fourth lines. Marc-Andre Cliche will center the third line with Cody McLeod and Maxime Talbot, while Brad Malone will center the fourth line with David Van Der Gulik, who was recalled from Lake Erie of the American Hockey League, and Patrick Bordeleau.
Colorado is 3-1-1 in the first five games of a seven-game homestand and coming off that disappointing loss to the Flames.
"You always want to bounce back from a game like we played against Calgary," coach Patrick Roy said. "It will be important for us to finish the homestand on the right foot. We want to play well tonight, there's no doubt about it. We're playing a team that won their last four games and they're coming here with a lot of confidence."
MacKinnon was hit with a puck near the end of the game Monday and didn't practice Tuesday.
"I'll be all right," MacKinnon said. "Hockey players are tough. But I'm all good. It was just a day I had to get it healed up and I'm good to go."
The Senators have outscored teams 15-10 during their four-game winning streak and opened a three-game trip Saturday with a 4-3 overtime win against the Montreal Canadiens.
"I had some good memories here," he said. "This was the first organization that gave me a shot to be a No. 1. This building, these fans and the organization means a lot to me, but things change and you move on and now we've got to beat them.
"We're definitely looking forward to this game. We've been playing well of late, we've won some games and we want to make sure that we keep that going."
Here are the projected lineups for the Senators and Avalanche:
Injured: Chris Neil (hamstring)
Notes: Tanguay took part in the morning skate, the third day in a row he has skated. Tanguay has been sidelined since sustaining knee and hip injuries Nov. 2 against the Montreal Canadiens. "He looked good," Roy said. "Things are going well for him. We're behind him on this and the only thing we can do is support our players. Alex seems comfortable right now." Tanguay remains on injured reserve and is out indefinitely.