Letang, third among NHL defensemen in scoring with 54 points, left with 4:45 to play in the second period after a hit from Arizona Coyotes captain Shane Doan. Letang, in the corner behind his net, was shoved backward by Doan after flipping the puck out of the zone.
"I just went to make sure I got a piece of him so he couldn't jump by me and he obviously went into the boards awkward," Doan said. "You never ever want to see anyone like that, especially a guy with his caliber and everything he's went through in the past couple years.
"You feel awful as a player when something like that happens."
Penguins coach Mike Johnston said Letang was evaluated at a local hospital.
"We'll get an evaluation as to where everybody thinks he's at in the morning," Johnston said. "Kris Letang is a premier player in the league and he's had a phenomenal season for us.
"I saw Kris lying on the ice and when I saw him come off, it didn't look good."
Letang, who has a history of concussions and suffered a stroke last year, fell awkwardly with the back of his head hitting the end boards. He remained on the ice for several minutes with the trainer and team doctor before he left the ice with help from teammates Steve Downie and Rob Scuderi. Downie stuck up for his downed teammate when he and Doan fought soon after.
"I have nothing but respect for (Doan)," Downie said. "That's hockey right there.
"(Doan) is not like that. I don't think that was dirty. I think (Letang) fell the wrong way and the distance from the boards and everything. We talked about it and I said, 'Hey, it's kind of got to be done,' and he's not going to shy away from that."
Downie provided perhaps the biggest lift in the third period, teaming with Crosby for power-play goals 2:05 apart to give the Penguins the lead for good. They won 3-2.
"A lot of adversity, but it's a good thing and we got the win," Downie said.
The Penguins welcomed Evgeni Malkin and Patric Hornqvist back to the lineup Saturday. Malkin missed six games with a lower-body injury and Hornqvist five with an undisclosed ailment before returning on Saturday.
Now, they may be without another star player in Letang.
"It's tough because we finally get two key players back and we lose another," Downie said.
The Associated Press contributed to this report.