Defenseman John Moore, who missed the past six games recovering from a concussion, will replace McDonagh, who was injured Tuesday on a hit by Vancouver Canucks forward Alexandre Burrows in the Rangers' 3-1 win.
McDonagh, who is listed as day-to-day, is among the NHL's top-scoring defensemen with 14 goals and 29 assists in 77 games. He leads the Rangers in ice time, averaging 24:49 per game.
"I don't think it's going to be very long," Rangers coach Alain Vigneault said of McDonagh's absence after the morning skate. "His 25 minutes are big minutes against big lines and on the power play and penalty killing, so we're going to try and spread those minutes around, and I'm confident our group will be able to get the job done."
Moore, who has three goals and 10 assists in 69 games, will play his first game since getting injured March 21 against the Columbus Blue Jackets.
"John hasn't played in a while, so we'll probably mix and match," Vigneault said. "He's a highly skilled defenseman, a great skater with a great shot. He's got a great set of tools, and hopefully by playing he'll become even better."
Moore is eager to return to the lineup, though he wishes the circumstances were different.
"It's tough to lose a guy like [McDonagh], but I can't really worry about that," he said. "I only worry about what I can control, and that's how I play tonight."
New York (43-30-4) is in second place in the Metropolitan Division, has five games remaining and is close to clinching a spot in the Stanley Cup Playoffs. The Rangers lead the third-place Philadelphia Flyers (39-27-9) by three points but have played two more games. The Rangers are 2-1-0 in the first three games of a four-game road trip and have won seven of their past eight games.
Colorado (48-21-6) is second in the Central Division and has clinched a postseason berth. The Avalanche, who have won four consecutive games, lead the third-place Chicago Blackhawks (42-19-15) by three points and have a game in hand.
Goalie Semyon Varlamov will start for the Avalanche with a chance to tie former Colorado goalie and current coach Patrick Roy's franchise record of 24 home wins set in 2000-01. Varlamov has a 23-9-3 record at home. His career-high 38 wins is two shy of the franchise record, also set by Roy in 2000-01.
"I was thinking of not playing him," Roy said, joking. "Hopefully he does it. Hopefully he's going to tie it tonight and pass it Sunday [against the Pittsburgh Penguins]. I'd be very happy."
Here are the projected lineups for the Rangers and Avalanche: