The 20-year-old has made three appearances for Ronald Koeman's side at the start of the 2021-22 campaign, featuring in the La Liga clashes with Real Sociedad, Athletic Bilbao and Getafe.
The right-back has now emerged as a major doubt for Barcelona's next game on September 14, though, which comes against Bayern Munich in the Champions League.
"Tests conducted this Wednesday by the FC Barcelona Medical Services have revealed that Sergino Dest has sprained his right ankle. He picked up the injury playing for the United States against Canada in Nashville last September 5 and is currently unfit to play," read a club statement.
Dest has been an important player for the Catalan giants since arriving from Ajax last October, making 44 appearances during his first season at the club, contributing three goals and one assist.
Barcelona had been due to face Sevilla in La Liga this weekend, but the fixture has been postponed due to the late-returning South American players from international duty.