The Ducks placed Despres on waivers Friday. General manager Bob Murray indicated the club will buy out the remainder of his $18.5 million contract.
Despres was just one game into his five-year contract extension last fall when the Ducks lost him for the entire season with his third apparent head injury in 12 months.
"Simon Despres is a good hockey player and a good person,'' Murray said in a statement. "But at this point in time, we feel it is in the best interests of both Simon and the organization to part ways. We wish him the very best in the future.''
Despres earned his contract extension with outstanding play for Anaheim late in the 2014-15 season after arriving in a trade with Pittsburgh. The Penguins' first-round pick in 2009 couldn't land a steady NHL role until he excelled with the Ducks, who finished one game shy of the Stanley Cup Final that spring.
But Despres missed 42 games during the 2015-16 season with a concussion from an illegal hit by Colorado's Tyson Barrie, and he was hurt again by a hit to the head in March 2016.
Despres was injured yet again in the Ducks' season opener in Dallas last October. Although Despres attended several playoff games and even skated before practice last month, he never appeared to be close to returning to action, even while the Ducks returned to the Western Conference finals.
On Twitter, Despres thanked the Ducks "for a wonderful 2 and a half years. I wish my teammates all the best moving forward.''
Anaheim has disclosed few details about Despres' health during the past two seasons, other than to affirm Despres' struggles with head injuries. Murray didn't mention Despres' concussion problems in a brief statement announcing the move, and nobody has speculated on whether Despres will play hockey again.
A buyout would keep Despres on Anaheim's payroll until 2025, but only at a total cost of just over $5 million. The move is financially friendly for the budget-conscious Ducks, who will gain flexibility under the salary cap by reducing Despres' payday.
The Ducks are maneuvering to keep together their talented young corps of defensemen. All-Star blueliner Cam Fowler is working on a long-term contract extension, while three promising defensemen will be restricted free agents next summer: Josh Manson, Brandon Montour and Shea Theodore.