The 23-year-old was attempting to bring the ball down between two Revolution players in the middle of the pitch when he went to ground clutching his ankle. He was helped back to the dressing room for further treatment by two of the medical staff, and departed the stadium on crutches and wearing a protective boot on his left foot, returning to the team's base in a vehicle away from his teammates.
Gareth Southgate will also be anxious about the 23-year-old's fitness, with his England squad for the Nations League next month being announced on Thursday.
But Loftus-Cheek's ankle injury soured what was an otherwise comfortable outing for Chelsea.
While supportive of the good intentions around the friendly fixture, which raised around £3.1m to combat discrimination with around 27,000 attending the match, Sarri had been unconvinced as to the timing of a game tagged on to a draining season.
Chelsea were due to give their players four days of holiday after the game at Gillette Stadium, but now it seems Loftus-Cheek will be forced to head straight for the treatment room.
Two goals from Ross Barkley and one from Olivier Giroud secured a 3-0 victory, while youngsters Conor Gallagher, Reece James and Trevoh Chalobah were handed minutes by Sarri. The midfielder has enjoyed the best form of his Chelsea career since overcoming the latest bout of back trouble and has been a driving force through the midfield over recent weeks and contributed 10 goals in all competitions. Four of those came in the Europa League, in which he has been a regular.