Spezza hurt his left knee Thursday night when he was checked into the boards by Martin St. Louis with six minutes left. He did not return to the game.
Spezza walked with a limp Friday and said he has "no idea" when he'll be back. This is his first knee injury.
"I'm definitely frustrated," he said. "The back's starting to feel better. One thing starts feeling better and this happens. But it's part of the game."
Spezza said the hit was harmless, and coach Bryan Murray agreed.
"It was just a body check," Murray said. "It's a freaky thing. I'm not sure how he caught his leg."
Spezza was off to a blistering start, leading the team with 44 points (19 goals, 25 assists) in 36 games. The 19 goals are just three short of his career high set in 2003-04. He ranks eighth in league scoring.
"It is frustrating, obviously," Murray said. "You lose a guy like Jason that is a key guy on our hockey team as far as getting points, running the power play, things of that nature."
The Senators (17-18-1) are 12th in the Eastern Conference and have just five goals in their past four games (1-3-0).