Puel's side are in a battle for the top three in Ligue 1, but will now have to do so without 16-year-old sensation Maupay, who is undergoing surgery on Wednesday for a ruptured cruciate ligament.
"It's a bitter blow for Neal and for us as we needed everybody for the final few matches of the season," Ligue1.com quotes Puel as saying.
"The injury didn't seem serious and he carried on playing before going off.
"We've tried to protect him in terms of his amount of game time and the media pressure. At least now he'll be able to prepare for his school exams in peace."
Nice are currently fifth but are just two points behind third-placed Lyon.