Results from an MRI on Monday confirmed Collins' injury, and Bears coach Marc Trestman said the defensive tackle is out for the season.
Collins will undergo surgery in the next two weeks in Chicago and faces an eight-month rehabilitation process.
"Nate Collins is bad. He's got a torn ACL," Trestman said. "It's a Henry Melton thing. He'll let it settle for a week. Then he'll have surgery ... I'm very disappointed."
Coincidentally, Collins was filling in for Melton as a starter at defensive tackle.
The Bears entered Sunday's game already down another starting defensive tackle in Stephen Paea, who was inactive due to turf toe. Paea said after the game that there's a good chance he'll play Thursday against the New York Giants.
Trestman echoed that sentiment, but he also remains leery of rushing Paea back into action too early.
The Bears will continue to search for depth at defensive tackle and will likely bring in several players for tryouts Tuesday at Halas Hall. The Bears signed Landon Cohen just two days prior to their Sept. 29 matchup at Detroit, and he contributed against the Lions.
In the loss to the Saints, the Bears lined up with starting defensive end Corey Wootton and Collins as the starting defensive tackles, and also plugged defensive end David Bass and Cohen into the rotation.
"It's the National Football League, and it's the next man up," Trestman said. "We all know the guys we have here. We'll continue to look around and see what's out there. We'll know more about that today. Yesterday, I thought that Corey did a good job for the first time inside. Landon made some plays. We've got to continue to mix it up. We'll continue the moves and try to do things structurally to try to get a push inside."
As it stands, the Bears have just three bona fide defensive tackles on the roster in Paea, Cohen and undrafted rookie Zach Minter, who was active Sunday but didn't play. Trestman said the staff will explore the possibility this week of giving Minter playing time.
Minter hasn't played in a regular-season game.
"We've been working hard to develop him," Trestman said.