The 21-year-old has left the France squad after returning a positive test the day before their Nations League match against Croatia.
The former Monaco man had been expected to play against Croatia, having shaken off an ankle injury sustained in the 1-0 win over Sweden last week.
"Kylian Mbappe will miss the game against Croatia," France confirmed in a short Twitter statement on Monday.
"His COVID-19 test - carried out by UEFA this morning - was positive, and he was isolated from the rest of the squad."
Goalkeeper Steve Mandanda and midfielder Houssem Aouar had already left the France squad after testing positive for COVID-19.
Meanwhile, PSG have had six confirmed cases of the virus from among those players who are going through pre-season preparations.
Thomas Tuchel's side are due to begin their Ligue 1 title defense against Lens on Thursday in a match that has already been pushed back after PSG reached the Champions League final in August.