The forward, who played 20:30 in a 5-2 loss to the Anaheim Ducks on Saturday, is the second player on Colorado's top line to be sidelined because of injury. Mikko Rantanen (lower body) has not played since Oct. 21 and is week to week.
Landeskog will be out "longer than week to week," Avalanche coach Jared Bednar said after practice Tuesday.
"[Landeskog] got hurt over the last couple games, came to practice Sunday, had some discomfort, and he went for further evaluation," Bednar said. "He has a lower-body injury, and he's going to miss some significant time here. I really don't have a timetable on him."
Landeskog has seven points (three goals, four assists) in 11 games this season and 423 points (180 goals, 243 assists) in 590 NHL games in nine seasons, all with Colorado, which selected him with the No. 2 pick in the 2011 NHL Draft.
Colorado will retool its top line with forwards Nazem Kadri and Joonas Donskoi flanking center Nathan MacKinnon, Bednar said.
The Avalanche (8-2-1) host the Florida Panthers on Wednesday (10 p.m. ET; ESPN+, ALT, FS-F, NHL.TV).
"Everybody has to play their best, like always," MacKinnon said. "Obviously, missing Gabe and Mikko, we're a worse team. Hopefully, we can kind of weather the storm for a few weeks until they get better."
Kadri, who has seven points (five goals, two assists) in 11 games, had been center on the second line with Donskoi and Andre Burakovsky.
"I think I understand the way Nate wants to play and his tendencies," Kadri said. "I think we'll be able to generate some chemistry on the ice, and hopefully that leads to some success. With a couple guys out, there's some minutes on the table for people to take advantage of. We've been talking about how good our depth has been all year, and now's a perfect example to show it.
"We're not going to sit here and feel sorry for ourselves. Obviously, those are hard guys to replace, and I'm not sure we can replace them, but we have good enough guys in this dressing room to be able to step up and answer the bell and produce."
Tyson Jost, who had been playing center on the third line, will move up to the second line with Burakovsky and J.T. Compher. Vladislav Kamenev, a healthy scratch the first 11 games, was the center on a line with Valeri Nichushkin and Colin Wilson on Tuesday.
Bednar said Wilson "tweaked something" and will not play against the Panthers. The Avalanche are expected to call up a forward from the Colorado Eagles of the American Hockey League.
"We have guys that want to prove we can have success without some of those guys in the lineup," Bednar said. "It's disappointing that they're out, but this is something you have to work through. You look at Pittsburgh, they lost (Evgeni) Malkin, they didn't hang their heads. They have other players stepping up in meaningful roles and they've continued to have success. Every team is going to go through it at some point."
