At least 42 people, including a child, were killed when militants launched four suicide car bombings at security targets in Mukalla, a southeastern port city in Hadramaut province.
Most of the killed were soldiers.
At least 30 more people were also wounded, all security officers except for five civilians, two senior government officials told CNN.
One of the attacks targeted a military compound near a government intelligence building. The others targeted military checkpoints. A child walking near one of the checkpoints was killed.
ISIS has claimed responsibility for these attacks.
Amaq, a media voice of ISIS, said in a statement published on Twitter that four ISIS attackers targeted a joint security base.
The areas attacked had been mostly controlled by Al Qaeda in the Arabian Peninsula (AQAP) and ISIS before government forces started a campaign to wipe them out.
These militant groups have responsible for at least 40 attacks over the last three months alone in Hadramaut, the Defense Ministry said.
Yemen has become a proxy battleground for Saudi Arabia and Iran. Yemen’s minority Houthis, who are Shiite, rebelled last year against the Sunni-led government of President Abdu Rabu Mansour Hadi, which is backed by Saudi Arabia.
A Saudi-led coalition got involved in march 2015 by launching airstrikes in support of Hadi against rebel targets in Yemen. Thousands of civilians have been killed in the violence.
Government forces and the Saudi-led coalition also have fought against AQAP and ISIS, both of which are anti-government Sunni terror groups.