The blast happened in the Balili mosque where Houthis who control Sana'a go to pray, according to witnesses.
Witnesses reported that after a first blast inside the mosque, a suicide bomber detonated an explosives belt at the entrance as worshippers rushed outside, AFP reported.
There was no immediate claim of responsibility but Sana'a has been shaken by a string of bombings by the ISIL terrorist group in recent months targeting Shiite followers.
The attack comes as Saudi-led coalition has ramped up air strikes against the impoverished Yemen, which started in March in a bid to restore power to fugitive former president Abd Rabbuh Mansur Hadi, a staunch ally of the Kingdom.
ISIL and the Yemen-based branch of its extremist rival al-Qaeda have exploited the turmoil to boost their activities in the impoverished country.