Police in Nice said the three suspects are believed to have broken into the hotel room occupied by an American employee of Swiss jewellery-maker Chopard in the early hours of Friday.
"We presume it was people specialised in this kind of theft," Philippe Frizon of Nice police, who are running the investigation, told AFP.
He said the three suspects entered the room through a door connecting it to an adjoining room while the Chopard employee was out for the evening and removed the small safe containing the jewellery.
The Chopard employee was questioned on Friday but is not considered a suspect, police said.