A local security official told the AFP news agency that the unmanned aircraft hit a car in the province of Hadramout.
He said the strike had killed two suspected al-Qaeda militants.
The Yemeni army is into the sixth day of an offensive to wrest control of cities in south Yemen from fighters reported to belong to al-Qaeda in the Arabian Peninsula.
Washington and Yemeni officials deny that drones are being deployed in Yemen.
However, US military specialists are closely involved in the Yemeni government’s campaign against militants.
And there are widespread reports that drones are being used.