The defenseman, who was injured in a 3-2 win against the Winnipeg Jets on Friday, is expected to recover in time for training camp next season. San Jose shut out the Minnesota Wild 2-0 on Saturday.
"Tough news, obviously one of our best players out again, but guys stepped up tonight in the back end and that was huge," Sharks forward Patrick Marleau said.
Karlsson, who led the Sharks with 40 points (six goals, 34 assists) in 56 games this season, missed 29 games last season because of a groin injury that also caused him to miss Game 6 of the Western Conference Final against the St. Louis Blues.
Sharks forward Tomas Hertl is out for the season because of a knee injury, and forward Logan Couture has not played since Jan. 7 because of a fractured ankle.
"Our leading scorer, with (two of) our other two leading scorers already out," San Jose coach Bob Boughner said. "It's a tough injury, it's more adversity for our club. It's going to have be a huge group effort. When you're missing three guys like that, not easily replaced."
The Sharks (26-28-4), who were eight points behind the Arizona Coyotes for the second wild card into the playoffs from the Western Conference, recalled defenseman Jake Middleton from the San Jose Barracuda of the American Hockey League. He has no points in four games with the Sharks this season and did not play Saturday.
"We're fortunate we've got [Tim Heed] who's been waiting to play all year and he's a really solid defenseman, so we're fortunate to have that depth, and guys stepped up tonight and filled those roles that need to be filled and did a great job," San Jose goalie Martin Jones said after making 39 saves Saturday.
NHL.com independent correspondent Jessi Pierce contributed to this report
