The overnight strike hit a vehicle parked near the presidential palace in Mukalla, capital of Hadramawt province, witnesses said.
The United States, whose intelligence agencies consider the Yemen-based Al Qaeda in the Arabian Peninsula (AQAP) to be the most dangerous branch of the jihadist network, is the only country that operates drones over the war-torn country.
On April 14, AQAP announced the death of one of its ideological leaders, Ibrahim al-Rubaish, in a similar drone strike in Hadramawt.
US Defence Secretary Ashton Carter has acknowledged that Al Qaeda is gaining ground but has vowed that Washington will keep up its battle against the group.
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