Guentzel, taking a cross-crease pass from Evgeni Malkin, scored his team-best 20th goal before falling forward awkwardly into the boards behind the Senators' net at 6:55 of the third period.
He appeared to avoid hitting his head full force, but rolled on the ice before getting up and skating off while favoring his right arm/shoulder.
Guentzel immediately went to the dressing room after getting his 200th career point.
"I hope he's not out long," said Evgeni Malkin, who scored for the Penguins in the first minute. "It didn't look good. But everyone understands it's hockey. It's tough. I need to play better next game if Jake doesn't play."
Penguins coach Mike Sullivan told reporters after the game that Guentzel is being evaluated by team doctors and that the club could have an update on him Tuesday.
"It was really scary," Sullivan said. "Those are always dangerous when you fall that distance from the boards. There's no status on him right now."
Guentzel, 25, had a goal and an assist in the game and leads Pittsburgh this season with 43 points. He was named as the Penguins' lone All-Star earlier Monday.
Information from The Associated Press was used in this report.