United have been informed Cavani, who moved to Old Trafford on a free transfer on deadline day, will have to stay in isolation until Sunday -- a day after the trip the St James' Park.
"Cavani is being forced to self-isolate due to COVID-19 guidelines following his arrival into the country from France which means he is unable to make his debut at St James' Park," a club statement said.
United play PSG on Oct. 20 in their first game of the Champions League group stage.
Cavani travelled to Manchester from Paris on Oct. 4 and according to the United Kingdom's government rules has to spent 14 days in isolation.
He is training at home but has not played a competitive game since his last appearance for PSG on March 11.
He has not been part of a high-performance bubble since becoming a free agent and is therefore not exempt from the UK's quarantine rules.
Cavani, who has signed a two-year deal, had revealed he tested positive for coronavirus during the summer after a holiday in Ibiza.