Residents and local sources said the incident took place in Shabwah’s al-Naqba area on Friday.
Meanwhile, Yemeni officials, who were speaking on condition of anonymity, said the US missile had targeted a vehicle while it was driving and killed all its occupants.
The officials identified the victims as al-Qaeda militants, saying one of them was close to Saad al-Awlaki, the al-Qaeda leader in Yemen.
Over the past few months, Washington has stepped up its drone strikes against what are claimed to be al-Qaeda targets in Yemen.
Back in March, US President Donald Trump gave the Central Intelligence Agency (CIA) new powers to launch drone attacks against suspected terrorist targets. The authority was limited to the Pentagon under the former US administration.
The US also conducted deadly ground and aerial raids on Yemen in January and May, leaving dozens of Yemeni civilians dead in total.