The military officials from Shabwa province said that an unmanned U.S. drone carried out the attack on a vehicle carrying seven militants in the district of Azan. The officials said four were killed, while three were critically wounded and under treatment in a nearby Al Qaeda-run clinic in Shabwa.
A security official said the attack may have killed leading figures in the group, who were attending Friday prayers and left together. He had no further details.
A second airstrike on Friday, just a few kilometers from the first strike, hit a building believed to be used by Al Qaeda near a main market in the town of Azan. Four residents were wounded, said medical officials.
There was no immediate comment from U.S. officials, but Washington has carried out deadly airstrikes in Yemen in the past. Last year, a U.S. drone strike killed U.S.-born militant cleric Anwar al-Awlaki and a second American, Samir Khan, who edited Al Qaeda's Internet magazine.
Last month, Al Qaeda-linked militants publicly executed a Yemeni in Azan who they suspected of collaborating with the United States by planting electronic devices that help U.S. drones strike militant positions.
Al Qaeda in the Arabian Peninsula, as the branch is known, was believed to have plotted two failed attacks on American soil.
The group has taken advantage of a year of turmoil in Yemen to seize control of several regions in the south. Militants overran cities as the government focused its efforts on protecting the regime in the capital during a year of protests against former President Ali Abdullah Saleh.
Saleh's replacement, Abed Rabbo Mansour Hadi, has made fighting Al Qaeda one of his top priorities, but many Yemenis accuse the ousted president, whose loyalists are still influential in the military and in government bodies, of undercutting security operations and the new president's authority.
Also on Friday, suspected Al Qaeda militants opened fire on a powerful tribal sheik who sits in Yemen's upper house of parliament as he was coming out of a mosque in the southern city of Aden. His two bodyguards were killed in the attack but he was unharmed, according to medical officials.
Mohammed Hussein Ashal's tribe fought Al Qaeda last year in Mudya district in Abyan province near Aden, kicking them out of several towns.
Militants killed Ashal's son last year in the capital Sanaa, and have also targeted other officials in Aden, shooting dead an intelligence chief in December.
All officials spoke on condition of anonymity because they were not authorized to speak to media.