The departure of Justice Minister Francois Bayrou and others from the MoDem party comes amid a funding scandal.
It is an embarrassing blow for a new French government pledging to battle political sleaze.
Justice Minister Francois Bayrou, who is spearheading the drive, quit because of scandal on Wednesday.
He and other centrist allies of President Emmanuel Macron, from the MoDem party, have stepped down amid a judicial investigation into claims it misused EU parliamentary funds.
— The Local France (@TheLocalFrance) 21 juin 2017
While those concerned deny wrongdoing, the departures, including European Affairs Minister Marielle de Sarnez, cast a shadow over Wednesday’s cabinet reshuffle by the government dominated by Macron’s new Republic On the Move (LREM) party.
Conservative rivals The Republicans had on Tuesday called for Bayrou and de Sarnez to quit over the investigation into MoDem.
On Monday, the government announced that Richard Ferrand, a minister for territorial planning and key member of LREM was leaving to chair the party’s group in parliament. He is the target of a separate judicial probe.
Being a target of a preliminary investigation in France is not an indication of guilt. Prosecutors can decide to either drop the probe or proceed to a full-fledged investigation
Macron, elected on an independent centrist ticket on May 7, had crafted a first government that comprised ministers of the left, right and centre, reshaping France’s political landscape as he extended his support base.
In parliamentary elections on Sunday, his LREM party won 308 seats in the 577-strong National Assembly, while MoDem gained 42.