Crosby, who leads the Penguins with 72 points (26 goals, 46 assists) in 59 games this season, did not take pregame warmups and was not present for an optional morning skate. He was a full participant in practice on Wednesday.
Evgeni Malkin replaced Crosby on the first line with left wing Jake Guentzel and right wing Bryan Rust. Jeff Carter shifted from right wing to Malkin's usual spot at center on the second line.
The Penguins (41-20-10) are third in the Metropolitan Division, four points behind the Rangers for second and six behind the Carolina Hurricanes for first. They lost to the Rangers 5-1 on March 25 and 3-2 on March 29.
Defenseman John Marino and forward Radim Zohorna also didn't play because of non-COVID illnesses.
Marino has 24 points (one goal, 23 assists) in 71 games this season. Zohorna has six points (two goals, four assists) in 17 games.