The Italy international, who has scored 11 times in 28 caps, was injured after scoring and providing an assist in a 2-2 draw with Al Shabab on Tuesday.
"Medical examinations have confirmed that Mateo Retegui has sustained a distal tibial fracture," Al Qadsiah posted on X.
"He is set to undergo surgery in the coming days and will be ruled out for the remainder of the season," the club added.
The 26-year-old Retegui, who was born in Argentina, scored 16 goals in 28 SPL games this season. He was part of the Italy national team that lost against Bosnia and Herzegovina in the 2026 World Cup playoff final last month.
Brenden Rogers's side, Al Qadsiah, are fourth with 62 points from 29 games, four points behind Al Ahly, who have a game in hand. The top three teams will qualify for next season's Champions League Elite.