Howard was hurt Monday night during the second period against the St. Louis Blues.
Detroit coach Mike Babcock says Jonas Gustavsson will start in Howard's place Wednesday night against Chicago.
"It's a big loss," backup goalie Petr Mrazek told the team's website. "We have to think of the positive and play the same game."
Howard sprained a ligament in his left knee two months ago and missed eight games. He returned in time to be named to the U.S. team for the Winter Olympics. Howard insists he is not concerned about missing the Sochi Games.
Tampa Bay's Ben Bishop, who ranks among the NHL's best goalies this season, would likely replace Howard if he isn't healthy enough when the Americans have to set their final roster on Feb. 11.
Howard's situation is another health setback in a season full of them for the Red Wings, who are likely to be without Pavel Datsyuk for an eighth straight game and Daniel Alfredsson for a sixth consecutive contest. Johan Franzen has been out since mid-December with a concussion, though defenseman Jonathan Ericsson could return Wednesday after missing the last 10 with a rib injury.