The suspected militants were travelling in the Al-Musaina region of Shabwa when their vehicle was hit, the official said.
The car was burned out and all three suspects on board were killed, he added.
On Friday, a similar drone attack in Shabwa killed four suspected members of Al-Qaeda, according to a security official.
US strikes have taken out a number of senior Al-Qaeda commanders in Yemen over the past year.
Washington considers the Yemen-based Al-Qaeda in the Arabian Peninsula to be the network’s deadliest franchise and has vowed no let-up in its war against the jihadists.
AQAP has exploited the power vacuum created by civil conflict in the impoverished Arabian Peninsula country to expand its presence in the south and southeast.