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.
Yemen has been convulsed by unrest since the Huthis seized Sanaa in September 2015.
Islamist militants, including Al-Qaeda in the Arabian Peninsula and the Islamic State jihadist group, have also established a foothold in and around the main southern city of Aden.
