Crosby was a surprise late scratch after he participated in the pregame warmup.
"I would say it's not an injury," Penguins coach Mike Johnston said. "He didn't get himself injured in the warmup. He just wasn't feeling well and went to see the doctors."
The Penguins lost their other star centre when Malkin appeared to sustain a lower-body injury after colliding with Bruins forward Chris Kelly during his first shift.
Pittsburgh's second-leading scorer limped to the dressing room, returned to the bench midway through the first period but was absent after the first intermission.
Johnston did not specify the nature of Malkin's injury, but he said Malkin and Crosby "might be able to play" Sunday against Detroit.
Crosby, among the NHL's leading scorers with 70 points, was replaced by Craig Adams, who joined the game during the first period after originally being listed as out of the lineup.
Malkin has 68 points this season and leads Pittsburgh with 28 goals.