The veteran striker, 35, started and played 79 minutes of Uruguay’s 2-0 World Cup qualifying victory over Chile on Tuesday night.
However, Cavani was replaced late on by Luis Suarez at the Estadio San Carlos de Apoquindo having limped off with an apparent calf problem.
He will now be considered a major doubt for United’s return to Premier League action against Leicester at Old Trafford on Saturday evening.
Ralf Rangnick’s side also face Everton, Norwich, Liverpool and Arsenal in a crucial month as they desperately try to stay relevant in the race for a fourth-place finish term.
United currently sit sixth, four points adrift of Arsenal having played a game more, after a morale-boosting, Cristiano Ronaldo-inspired 3-2 win over Tottenham on March 12, with their subsequent meeting with rivals Liverpool re-arranged due to the Reds reaching the quarter-finals of the FA Cup.
United were sent packing from the Champions League earlier this month after Renan Lodi’s second-leg header secured a 2-1 aggregate victory for Atletico Madrid in the last-16.
Losing the experienced and valued Cavani again is a major blow for Rangnick, with the ex-Paris Saint-Germain stalwart having only made two brief substitute appearances since missing six matches due to a groin problem.
A tendon issue also kept him out between the start of November and late December, while he also missed six of the first seven games of the season due to more injury strife.
Cavani has played less than 800 minutes across all competitions for United in total this term after signing a one-year contract extension last May. He is set to leave the club when that latest deal expires in the summer.