The coalition still won a confidence vote 92-78.
The government called the vote in response to an opposition no-confidence motion after hauliers, farmers and agricultural workers blockaded oil infrastructure and left about a third of Ireland's petrol stations without fuel last week.
But the loss of support was an unexpected blow.
The defections signal growing strain on the coalition of Fine Gael and Fianna Fail, which relies on independent MPs for its slim majority.
With global fuel prices expected to remain high, the government faces the prospect of further public anger.
The disruption ended on Monday after ministers announced 505 million euros ($A835 million) in spending increases and tax cuts to soften the effect on consumers and businesses, on top of a 250 million euro package introduced three weeks ago.
However, junior minister for agriculture Michael Healy-Rae said that was not enough and resigned from his role.
His brother and fellow rural independent MP, Danny, also voted against the government, further cutting its majority.
"Because of the fact that I believe this government has let the people of Ireland down, I will be voting no confidence in the leader of the country and I will be tendering my resignation," Michael Healy-Rae told parliament.
A group that had gathered outside parliament to protest against the government cheered him when he later spoke to reporters.
Prime Minister Micheal Martin earlier rejected accusations that the government was not providing enough support and said the funding to date was proportionately the largest assistance package of any European country.
The Healy-Raes were among nine independent MPs whose support helped the conservative parties of Fine Gael and Fianna Fail return to government just over a year ago.
Martin can now only rely on the support of 92 MPs, with 87 seats required for a majority.
"They still have a reasonable majority and the lesson of history of Irish coalition politics is that governments tend to endure but the big question left is what they can achieve in the face of these ongoing global challenges," said Theresa Reidy, politics professor at University College Cork.
Protests in Ireland began on Tuesday last week with slow-moving convoys clogging roadways.
They grew as word spread on social media as truckers, farmers and taxi and bus operators blocked key infrastructure and the main thoroughfare in the capital Dublin.
Demonstrators called for price caps or tax cuts to alleviate soaring fuel costs they said will drive people out of business.
Martin said the government can learn from the protests but defended the response by police and military to clear roadblocks at the country's sole oil refinery at Whitegate in County Cork and at several depots.
with AP