An army official spoke of three suicide bombings and held rival jihadists of Al-Qaeda responsible, but an IS statement posted online said one of its militants was behind the attack.
It was a rare intervention by IS in the city which was held by rival jihadists of Al-Qaeda for a year until they were driven out by government troops last month.
‘A knight of the knights of martyrdom, brother Hamza al-Muhajir... was able to detonate his explosives-laden car at a post of the apostates of the militia of (President Abedrabbo Masour) Hadi,’ the IS statement said.
Several soldiers were also wounded in the attack on the eastern outskirts of the Hadramawt provincial capital, the military official said.
The deadly assault came shortly before Prime Minister Ahmed bin Dagher arrived in Mukalla with several ministers on a one-day visit aimed at reviving government institutions in the city, a local official said.
One suicide bomber rammed a vehicle packed with explosives into the gate of a base in the Khalf district, followed immediately by a second who blew up a car in the centre of the camp, the military official said.
Jihadists clashed with soldiers outside the base immediately after the bombings.
A third suicide bomber targeted the nearby residence of the commander of Hadramawt's second military region, General Faraj Salmeen, but he escaped unharmed, the official said.
The commander of the province's first military region, General Abdulrahman al-Haleeli, survived a suicide bombing against his convoy on Wednesday that killed four of his guards.
Al-Qaeda was driven out of Mukalla and nearby coastal towns last month with support from Emirati and Saudi special forces.
The Pentagon revealed last week that ‘very small number’ of US military personnel has also been deployed around Mukalla in support of the operation to retake the city.
The US Navy also has several ships nearby, including an amphibious assault ship called the USS Boxer and two destroyers.
‘It does not serve our interests to have a terrorist organisation in charge of a port city, and so we are assisting in that,’ Pentagon spokesman Navy Captain Jeff Davis said.
The offensive against Al-Qaeda comes amid a truce and peace talks between the government and Iran-backed rebels it has been fighting with support from a Saudi-led coalition since March last year.
Jihadists of both Al-Qaeda and IS took advantage of that conflict to expand their presence in Hadramawt and other areas of the south, including second city Aden where the government has its base.
IS has claimed several attacks on government and coalition targets in Aden in recent months.
Washington regards Al-Qaeda's Yemen-based branch as its most dangerous and has stepped up a longstanding drone war against the group in recent weeks.
But the jihadists retain a strong presence in the southeast and still control several towns in the interior valley of Wadi Hadramawt.