Al Shabaab was not immediately reachable for comment. It was not known who was behind the aerial strike but the United States has in the past targeted al Shabaab fighters.
Al Shabaab have staged many bomb and gun attacks in the capital Mogadishu in its bid to topple Somalia's Western-backed government and have also hit targets in neighbouring Kenya since Nairobi joined African Union peacekeeping forces in Somalia.
Police and residents said that what appeared to be a drone attack took place at Balad Amin, about 30 km to the east of Wanlaweyn in the lower Shabelle region on Saturday night.
"We heard three big crashes at an al Shabaab base in Balad Amin last night. It looked like a drone but we have no news of casualties," Adan Ahmed, a resident of the area, told Reuters.
"The drone targeted an al Shabaab base last night. So far we have the information that five fighters including the al Shabaab leader in charge of Lower Shabelle region died in the strike," Major Abdiqadir Ahmed, a police officer based in Wanlaweyn, told Reuters.
In March, the U.S. Defense Department said a drone strike in southern Somalia killed Adnan Garaar, an al Shabaab leader believed to be the architect of a 2013 attack on a Nairobi shopping mall that killed 67 people.
Al Shabaab wants to impose its own radical brand of Islam on the Horn of Africa country.
The Jihadists were pushed out of Mogadishu by AU forces in 2011 but have continued attacks, often going after politicians and officials in Somalia, as well as AU and Somali forces.
Another of al Shabaab's attacks in Kenya was an assault on Garissa University College in April that killed 148 people.