"At this time, we are aware of and can confirm two US citizens were killed in the attack in Nice on July 14, 2016," spokesman John Kirby said.
"We express our sincere condolences to the family and friends of those killed."
The statement was issued as US Secretary of State John Kerry was in Moscow for talks on Syria with his Russian counterpart.
Kirby did not identify the two dead but added the United States was providing "all possible consular assistance" to its citizens.
A gunman drove a 19-tonne truck into a crowd of people celebrating Bastille Day last night in the French Riviera city of Nice in what authorities have called a "terrorist" attack.
Kirby's announcement came after US President Barack Obama strongly condemned what he said was a "horrific terrorist attack" and said the United States stood "in solidarity and partnership with France."
"Our embassy in Paris is making every effort to account for the welfare of US citizens in Nice," Kirby said. "Any US citizens in Nice should contact friends and family directly to inform them of their well being.
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