Tribesmen said a missile struck the vehicle in the Rafadh region of Shabwa province overnight, killing three.
A local security official said they were Al-Qaeda fighters.
The United States is the only country known to operate armed drones over Yemen.
It has kept up strikes on militants during months of fighting between pro-government forces and Shiite Huthi rebels who control the capital.
Amnesty International charged Friday that the Saudi-led coalition backing the Yemeni government had renewed its use of cluster bombs during a January air strikes on Sanaa that killed a 16-year-old boy.
The coalition has denied using such ammunition in its anti-Huthi attacks on the Yemeni capital.
Yemen has been convulsed by unrest since the Huthis seized Sanaa in September 2015.
Al-Qaeda’s local affiliate has exploited the turmoil to tighten its grip on parts of southeast Yemen, including Mukalla, capital of Hadramawt province.
Al-Qaeda in the Arabian Peninsula and the Islamic State jihadist group have also established a foothold in and around the country’s main southern city of Aden.
Late on Friday, unknown gunmen shot dead a police officer as he returned home in Aden, police said, in the latest in a string of such attacks in the city.