It was not immediately known whether the attack was linked to Thursday's presidential election, which the rebels boycotted. Sri Lanka's Muslim population, which is at odds with the rebels, voted in the election.
"Two grenades were thrown at the mosque that killed four people and wounded 10 others," said Deputy Inspector General of Police Nimal Lewke.
The Defense Ministry also confirmed the attack in Akkaraipattu in eastern Batticaloa district. There were at least 60 worshippers in the mosque, it said.
Sri Lanka's Muslims generally do not trust the rebels, who are mostly Hindus. During two decades of civil war, the rebels carried out systematic killings of Muslims, including a massacre in August 1990 of 130 Muslims at two mosques on the same day, as they tried to assert control over eastern Sri Lanka.
The rebels started fighting in 1983 for a separate Tamil homeland in the northeast. The war stopped after a 2002 cease-fire. The uneasy truce is holding, but peace talks have stalled, reported AP. P.T.