The forward immediately went to the bench and into the locker room and was later ruled out of the rest of the game with an upper-body injury.
Lupul, who signed a five-year, $26.25 million contract extension on Sunday, could miss significant time.
"(Thanks) for the support everyone," Lupul tweeted after the game. "I will be doing everything I can possibly do to be back as soon as possible."
In 66 games with the Leafs last season, Lupul posted 25 goals and 42 assists for 67 points.