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The Uruguayan picked up an injury in last week's game at Tottenham Hotspur, where he scored one of the goals in a 3-0 victory.
The 34-year-old also came off the bench in Tuesday's 2-2 draw away in Atalanta, but is set to miss the visit of Pep Guardiola's men on Saturday and join Raphael Varane and Paul Pogba on the treatment table.
The striker has also been excluded from Uruguay's squad for the upcoming World Cup qualifiers against Argentina and Bolivia.
"He will not play tomorrow. It will not be in order. He has had a very severe pain in a tendon for two days," said Uruguayan reporter Rodrigo Romano in quotes published by the Daily Star.
"That was the pain he felt [after 80 minutes] against Tottenham and that did not let him start against Atalanta. He is in recovery. He does not play tomorrow."
Cavani was feeling pumped ahead of the Manchester derby and told the United Review: "They are the kind of games that I think everyone, including me at least, wants to be involved in, because they are very special occasions. Games that remain part of history and stay in everyone's memory."
The striker's omission is a fresh blow for United, who know that a victory on Saturday will move them level on points with Man City.
'El Matador' has been a big hit since arriving at Old Trafford on a free transfer from Paris Saint Germain in October 2020.
He has scored 18 goals in 47 appearances for the Red Devils to date after a hugely successful spell with PSG, where he managed 200 goals in just 301 appearances.
United's match against City is their final game before the international break, ahead of a trip to Watford on 20th November.
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