The strike in Abyan province is the latest in a series of attacks on al-Qaeda targets in the troubled Arabian state, which is battling Islamists Ansar al-Sharia (Partisans of Islamic Law) who have won a string of victories over government troops.
This is part of the strategy to uproot al Qaeda from areas they control, a Yemeni aide told CNN.
The Yemeni government is giving the green light for the attacks and targets are chosen carefully.
Wednesday's drone strike follows similar attacks in Zinjibar and Lowder districts on Monday which killed seven militants.
According to the officials, these attacks will be followed by strikes on other targets in Abyan province over the next two weeks.
The Jaar, Lowder and Zinjibar districts will be hit with drone strikes, the official added.
Yemen's acting President Abd-Rabbu Mansour Hadi has faced severe challenges since taking office in February vowing to fight al Qaeda.
Only days into his rule, more than 100 government soldiers were killed in attacks.
And last month at least 57 Islamist fighters and Yemeni troops were killed after al Qaeda militants launched an audacious attack on an army base in the troubled Abyan region.
Members of Ansar al-Sharia were eventually beaten back by Yemeni troops and aircraft, which bombed a captured checkpoint at the base in Abyan province, about 75 miles (130 kilometers) from the port city of Aden.
The United States and Saudi Arabia have formed a close partnership with the beleaguered Yemeni government, with the Americans sending logistical support, experts and attack drones to aid the military in its fight against al Qaeda-inspired militants.