"Sheikh Wahid al-Balous was killed in a car bomb attack as he was driving on the outskirts of Sweida city," said Rami Abdel Rahman, head of the Syrian Observatory for Human Rights.
Abdel Rahman said a second car bomb struck near the hospital in the Dahr al-Jabal neighbourhood where the wounded were being taken, and that eight people were killed altogether.
Syria's official news agency SANA also said eight people had been killed and 22 wounded.
"Balous was the leader of the Sheikhs of Dignity group, which aimed to protect the Druze areas in Syria," said Malek Abu Kheir, a journalist from Sweida who knew him.
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The Sheikhs of Dignity the most powerful militia in the area and had fought fierce battles against the Islamic State jihadist group and Al-Qaeda's Syrian affiliate.
Balous opposed army conscripts from Sweida being sent outside the province, and often spoke out against both jihadist groups and the regime of President Bashar al-Assad, Abu Kheir told AFP.
Activists told AFP the protesters had the support of Balous.