The first minus was a result of a backhand shot from Ducks defenseman Brandon Montour in the left circle that got past Sharks goalie Martin Jones on the short side to give Anaheim a 3-2 lead at 8:02 of the third period. Karlsson was close to Montour, but the puck didn't touch his stick.
The second was from Carter Rowney's empty-net goal at 19:36 of the third period. That was Anaheim's 15th shot of the game. San Jose had 33.
Karlsson was also on the ice for Adam Henrique's power-play goal at 10:22 of the third period that extended Anaheim's lead to 4-2. He was too high in the zone, opening the slot for Henrique, but the goal required some tic-tac-toe passing by Rickard Rakell and Jakob Silfverberg.
"They scored a beautiful goal on the power play, there's nothing we can do about that one," Karlsson said. "Stuff like that is going to happen."
Karlsson wasn't rattled because he had no reason to be.
He was involved all night and looked comfortable in his role on the right side of defenseman Marc-Edouard Vlasic.
Karlsson helped San Jose create sustained pressure on its power play in the second period, when he was the only defenseman on a unit that featured forwards Evander Kane, Timo Meier, Logan Couture and Kevin Labanc.
He had his only shot on goal of the game during that power play. It was the Sharks' only shot on goal in 4:05 of power play time.
Karlsson played both of San Jose's power plays in the first period with Joe Thornton, Joe Pavelski, Couture and defenseman Brent Burns. They struggled to get into the zone and couldn't sustain possession when they did.
That coach Peter DeBoer went away from that group for San Jose's power play in the second, its last power play of the game, is an indication that he's going to tinker until he finds groups that fit.
For example, although it looks great on paper, it's possible Burns and Karlsson, both righties who are first (82) and third (71), respectively, in power play points among NHL defensemen since the 2015-16 season, won't mesh well together on the same power-play unit.
DeBoer isn't ready to make that judgment yet.
"You're going to see a lot of fluidity to that," DeBoer said.
Karlsson was effective at 5-on-5, especially in the defensive zone, where he stopped several Ducks' chances with good positioning and deft stick work. He helped the Sharks get out of their zone quickly and into the offensive zone, a big reason why they outshot Anaheim 33-15 and more than doubled the Ducks in total shot attempts, 71-34.
"I thought he was good," DeBoer said of Karlsson. "We did a lot of good things. We gave up 10 or 12 shots through most of the game. Created a lot of chances ourselves. Didn't finish. Didn't extend the lead when we had opportunities to, and that's what happens."
