Couillard will officially announce his candidacy next Tuesday or Wednesday, sources close to him told CBC's French-language news service.
The 55-year-old brain surgeon had been mulling a run at the party leadership since Jean Charest resigned from the post on Sept. 5, the day after the Liberals were defeated in the provincial election.
Couillard was first elected to Quebec's national assembly in 2003 and served as health minister from then until 2008, when he quit politics.
He has worked in a variety of capacities over the last four years, including as an advisory partner at an investment fund and as a member of the Security Intelligence Review Committee, the federal civilian body that provides oversight for CSIS, Canada's intelligence service.
Couillard's former cabinet colleague Raymond Bachand has all but announced he too will run for the Liberal leadership.
Others who might vie for the top job include former transport minister Pierre Moreau and former labour minister Lise Thériault.
The party executive is drafting rules for the leadership race and expects to have them ready by Oct. 15. Delegates at the party's general council meeting in Laval on Oct. 21 will then vote on the proposed rules.