The veteran striker, 35, started and played 79 minutes in Uruguay’s 2-0 World Cup qualifier win over Chile on Tuesday night.
However, Cavani was replaced late by Luis Suarez at the Estadio San Carlos de Apoquindo after limping off with an apparent calf problem.
He will now be seen as a major doubt for United’s return to the Premier League against Leicester at Old Trafford on Saturday night.
Ralf Rangnick’s side will also face Everton, Norwich, Liverpool and Arsenal in a crucial month as they desperately try to stay relevant in the hunt for a fourth place finish.
United currently sit in sixth place, four points behind Arsenal having played one game more, following a Cristiano Ronaldo-inspired 3-2 win over Tottenham on March 12, with their subsequent meeting with rivals Liverpool rearranged due to the Reds . reach the FA Cup quarter-finals.
United were expelled from the Champions League earlier this month after Renan Lodi’s return header secured a 2-1 aggregate victory for Atletico Madrid in the round of 16.
Losing the experienced and well-liked Cavani again is a huge blow for Rangnick, with the former Paris Saint-Germain stalwart having made just two brief substitute appearances since missing six games with a football problem. oldest boy.
A tendon problem also sidelined him between early November and late December, when he also missed six of the first seven games of the season due to other injury disputes.
Cavani has played less than 800 minutes in all competitions for United in total this season after signing a one-year contract extension last May. He is set to leave the club when this latest contract expires this summer.