The British public goes to the polls on 23 June to decide whether or not to retain EU membership, with some businesses joining the campaigns, but others preferring not to speak out at all.
Guillaume Herbette, who became MSLGroup CEO in August, has placed himself on the remain side.
Speaking to PRWeek UK, he said: "From a personal standpoint I would say it would be a disaster, from a business standpoint I would say it’s going to isolate the UK even more, which obviously we do not need and I don’t think the UK needs.
"On top of that, from a currency point of view I don’t think it would be a good thing because it would isolate the pound even further so I really think it could have a negative effect."
MSLGroup employs 3,000 people globally in more than 100 offices, and its 225 London staff are currently being moved into a single office.
Other Publicis Groupe-owned media and creative firms with London operations include Fallon London, Saatchi & Saatchi and Starcom.