The bomber struck during the main weekly prayers in Eastern Province, where assailants linked to the Sunni extremist Islamic State group (IS) killed seven members of the minority Shiite community in November.
The interior ministry said a suicide bomber detonated a bomb at the mosque in Kudeih, in the Shiite-majority city of Qatif, the official SPA news agency reported.
“An individual detonated a bomb he was wearing under his clothes during Friday prayers at Ali Ibn Abi Taleb mosque in Kudeih in Qatif,” the ministry spokesman said in a statement.
He did not give a specific casualty toll, only that several people were killed and wounded.
Shiite activists and witnesses gave conflicting tolls, with one saying four worshippers were killed and others speaking of 22 dead.
Qatif hospital issued an urgent call for blood donations and called in off-duty staff to cope with the high number of casualties, the activist said.
Naseema Assada, a resident of Qatif, said worshippers were celebrating the birth of revered Shiite Imam Hussein when the blast occurred.
“The people are very angry,” she said, adding that they tried to stop police from entering Kudeih.
Residents had feared such an attack was coming, she said, because the government was failing to curb hate speech on social media against the Shiite community which complains of marginalisation.
“We don’t want a repeat of what is happening in Syria or Iraq here,” she said, referring to the jihadist IS that has declared a “caliphate” in those countries.
“This is our country and we love it.”
The mufti of Saudi Arabia, the highest-ranking Sunni cleric, denounced the attack.
“It is a criminal act aimed at dividing the sons of the nation… and at sowing trouble in our country,” he said on state television.
The attack comes as a Saudi-led coalition has since March 26 been bombing Shiite rebels in Yemen who have overrun much of the country and forced the government to flee abroad.
Analysts said radical Sunnis in the ultra-conservative kingdom consider Saudi Shiites to be allies of the Yemen Huthi rebels.
“This (attack) was unfortunately only a matter of time,” said Frederic Wehrey, a Gulf analyst at the US-based Carnegie Endowment for International Peace.
Shiites have not joined in the “wave of Sunni nationalism” that has followed the Saudi-led campaign against the rebels in Yemen, and are considered by radical Salafists as a “fifth column” for the Huthis.
The interior ministry spokesman said Saudi Arabia would “hunt down anyone involved in this terrorist crime carried out by people seeking to undermine national unity.”
The website of Arryadh newspaper posted pictures showing bloodied prayer rugs and part of the ceiling of the mosque that had caved in.
First reports by witnesses said the suicide bomber appeared to be from Pakistan, but others said he was wearing traditional Afghan clothing.
Eastern Province is an oil-rich region populated by many Shiites. It has been rocked by sporadic protests and attacks on security forces since 2011.
In recent months Saudi police have made a string of arrests of Sunni extremists suspected of plotting attacks aimed at stirring sectarian unrest in the province.
Last November, gunmen killed seven Shiites, including children, in the eastern town of Al-Dalwa during the commemoration of Ashura, one of the holiest occasions of their faith.
Four men carried out the attack after killing a man from a neighbouring village and stealing his car to use in the shootings, the interior ministry said.
It said the assailants had links with IS, which considers Shiites to be heretics.
In April, authorities said they arrested 93 jihadists, including 62 suspected of links to IS who were plotting attacks to “incite sectarian sedition”.
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