Cavani is yet to complete his 14-day quarantine in England, having flown in from France to complete his deadline day move to join Ole Gunnar Solskjaer’s side.
The 33-year-old Uruguay international joined United on a free transfer after seven seasons with Paris Saint Germain.
France is on the UK’s list of countries whose travelers must go into a period of self-isolation upon arrival.
Cavani has not trained with Manchester United since completing the move.
A statement on the United website read: "Cavani is being forced to self-isolate due to the COVID-19 guidelines, following his arrival into the country from France, which means he is unable to make his debut at St James' Park."
The former Napoli forward could however be available to face his former club PSG, where he ended up as the club’s all-time top scorer with 200 goals, when United open their 2020/2021 UEFA Champions League group stage campaign at the Parc des Princes next week.
Manchester United will also be without forward Anthony Martial for the Newcastle game after he was sent off in the 6-1 defeat to Tottenham Hotspur before the international break.
The Red Devils are currently 16th on the Premier League table, having started the season with one win and two losses in their opening three games.
