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.
Yemen has been under regular US drone strikes, with Washington claiming to be targeting al-Qaeda elements while local sources say civilians have been the main victims of the attacks.
The country has also been rocked by a military campaign by Saudi Arabia since late March 2015. The US has been providing huge amounts of arms and military training to kingdom’s military.
The aggression, which allegedly seeks to restore Yemen’s former Saudi-allied government to power, has killed over 12,000 people, according to the latest tallies
Al-Qaeda has exploited the US-backed Saudi war on Yemen to enhance its terror activities in the impoverished country.