Damphousse said he is leaving the union in order to devote more time to the spa business he owns.
Le Scandinave Spa has locations in Mont-Tremblant, Que., and Collingwood, Ont., and Damphousse is planning to expand the business across North America.
"It's a decision I have been carefully considering for the last few months," Damphousse said Tuesday in a release. "I am going to be more involved with our corporate group on the overall project."
Damphousse, 39, ranks 42nd on the all-time NHL scoring list after collecting 432 goals and 773 assists for 1,205 points during his 18-year career with Toronto, Montreal and San Jose.
Damphousse, a former NHLPA player representative and vice-president, was a member of the negotiating committee that reached a collective bargaining agreement to end the NHL lockout.
"I am especially proud to have been a member of the collective bargaining team that worked hard to come up with solutions to reach a labour agreement that ended the past lockout," said Damphousse.
Damphousse, who was hired as the NHLPA's director of business relations in February 2006, said he's looking forward to the next phase of his life.
"I've been involved in the game of hockey, in one capacity or another, for most of my life," he said. "Hockey will always be in my blood, but a new chapter in my life is about to begin and I am looking forward to the challenge."