Short hasn't played since suffering the injury in the team's Week 2 loss to the Tampa Bay Buccaneers. General manager Marty Hurney said in a statement that Short will undergo surgery and will not return this season.
"KK has done everything he could possibly do to try to play these past two games," Hurney said, "but we have made the decision that it is in the best long-term interest of KK and the team that he undergo surgery to fix his shoulder and focus on his rehab and get ready for next season."
The loss of Short likely means a bigger role for Vernon Butler, a former first-round pick who was inactive the first two games. The Panthers promoted defensive lineman Bryan Cox Jr. from the practice squad to fill Short's roster spot.
Short, a two-time Pro Bowl selection who has 32.5 career sacks, had four tackles this season in his two games. Before this season he had missed just two games in career, both last season.
Short, who signed a five-year, $80.5 million contract in 2017, is under contract with the Panthers through the 2021 season.
ESPN's David Newton contributed to this report.