Hit by a shot from Sabres defenseman Marco Scandella, Crosby played on for 6 minutes, 42 seconds before leaving. Pittsburgh forward Bryan Rust left the game after he was hit in the hand in the third period.
"They both got hit with shots," Penguins coach Mike Sullivan said. "They are being evaluated now. We will probably have more definitive answers tomorrow morning."
The Sabres won the game 3-2 in a shootout, with Casey Mittelstadt scoring in the sixth round.
Tage Thompson also scored for Buffalo in the shootout. Thompson's goal in the second round drew Buffalo even, after Pittsburgh's Kris Letang opened the round by scoring on a wrist shot. Letang was the only Penguin to score in the shootout.
The two teams will open the regular season Thursday in Buffalo.