Mark Fitzgerald, the group's commercial director, and James Shurey, group publishing director of magazines for Homebase, Toni & Guy, Debenhams and De Vere Hotels & Resorts, left the company last week after more than six years to set up their own agency.
Publicis has promoted two group publishing directors, Alistair Young and Geri Richards, to the new role of joint-managing director.
The publisher has been without a managing director since May last year, when Jason Frost moved up to become chief executive, taking over from John Wisbey, who was promoted to senior vice-president for business integration on Publicis Worldwide's global HP account.
The publisher has scrapped the three publishing director positions, as well as the role of commercial director.
Fitzgerald's duties will be assumed by three ad sales directors, Ian Anderson, Phil Burroughes and Donna Price.
Frost said: "Fitzgerald and Shurey's departures have given us the opportunity to shake things up and give people new responsibilities. We've scheduled meetings with clients to fill them in on the changes going forward."
Publicis Blueprint is part of the Publicis Groupe, which also owns media agencies Starcom and ZenithOptimedia. It also produces magazines for Asda, Prudential, Toyota and Renault Vans.