A Yemeni news website said the car was driving on a main road in the al-Qatan district of Hadramoutprovince.
"The vehicle and its occupants were completely burned," the official told Reuters, giving no details on who the victims were.
The United States has stepped up drone strikes as part of a campaign against "Al Qaeda".
Human Rights Watch said in a detailed report in August that U.S. missile strikes, including armed drone attacks, have killed dozens of civilians in Yemen.
It highlighted what it said were six "unacknowledged" U.S. military attacks on targets in Yemen that had either clearly or possibly violated international law.