There was no immediate claim of responsibility but Sanaa has been shaken by a string of bombings by the Islamic State (IS) jihadist group in recent months targeting Shiites.
Thursday’s blast ripped through the Balili mosque where Huthi Shiite rebels who control Sanaa go to pray, according to witnesses.
It came as Muslims marked Eid al-Adha, the Feast of the Sacrifice, the most important holiday of the Islamic calendar.
Witnesses reported that after a first blast inside the mosque, a suicide bomber detonated an explosives belt at the entrance as worshippers rushed outside. It was not immediately clear if the first blast was also from a suicide bomber.
IS, a radical Sunni Muslim group which controls swathes of territory in Iraq and Syria, considers Shiites to be heretics.
— Khaleej Times (@khaleejtimes) September 24, 2015
IS bomb attacks targeting several Shiite mosques in Sanaa on March 21 killed 142 people. The group has also claimed attacks on mosques in Kuwait and Saudi Arabia.
The capital of Sunni-majority Yemen has been under the control of the Iran-backed Huthi rebels for the past year. The insurgents have also expanded their grip to other parts of the country.
Extremists exploit chaos
Pro-government forces backed by air strikes and troops provided by a Saudi-led Arab coalition have recently managed to wrest back some southern provinces, including the second city of Aden.
After six months in exile in neighbouring Saudi Arabia, President Abedrabbo Mansour Hadi returned to Aden on Tuesday with a vow to liberate the country from the Huthis.
The Saudi-led coalition launched air strikes against the rebels on March 26, and began a ground operation in July.
Hadi loyalists began an all-out offensive against the Huthis in the oil-rich Marib province east of Sanaa earlier this month, aiming to retake the capital.
The United Nations says around 5,000 people have been killed and 25,000 wounded, many of them civilians, since late March in Yemen.
Yemen has descended into chaos since the 2012 ouster of longtime strongman Ali Abdullah Saleh, and security has broken down since Huthi militiamen swept unopposed into the capital a year ago.
IS and the Yemen-based branch of its jihadist rival Al-Qaeda have exploited the turmoil to boost their activities in the impoverished country on the tip of the Arabian Peninsula.
Al-Qaeda has long been the dominant jihadist force in Yemen, located next to oil-flush Saudi Arabia and key shipping lanes, but experts say IS is seeking to supplant its extremist rival.
Al-Qaeda in the Arabian Peninsula (AQAP) controls parts of the vast southeastern province of Hadramawt, including the provincial capital Mukalla, which it is seized in April.
It has distanced itself from IS’s tactics, saying that it avoids targeting mosques to protect “innocent Muslims”.
The United States has waged a longstanding drone war against AQAP which it regards as the jihadist network’s most dangerous branch.