The Victoria MP announced Thursday she's quitting politics and returning to private life as of Aug. 31.
The 69-year-old cited a "health warning" from her doctor for her decision.
"My doctor gave me a health warning this spring and recommended that I adopt a more balanced lifestyle, without the travel and physical demands of the job of an MP from Western Canada," she said in a written statement.
NDP Leader Tom Mulcair was on hand for Savoie's announcement at her Victoria constituency office.
He said Savoie will be "missed by all of her colleagues regardless of political affiliation."
Savoie was first elected in 2006 and currently serves as deputy Speaker in the Commons.
Her resignation leaves the NDP with 101 seats and raises the possibility of as many as four byelections this fall.
Calgary Centre is vacant following the surprise resignation of Conservative MP Lee Richardson last spring.
The Toronto-area riding of Durham is also vacant following the resignation of Bev Oda, the beleaguered international co-operation minister.
A byelection may also be necessary in the Toronto riding of Etobicoke Centre, where defeated Liberal MP Borys Wrzesnewskyj successfully sought a court order to overturn the result of the 2011 election.
Tory MP Ted Opitz, who won the riding by 26 votes, has appealed the matter to the Supreme Court of Canada, which has yet to rule on the case.
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