Riot police in Addis Ababa firing at stone-throwing protesters killed five people and wounded 18, hospital sources said, in a new backlash against a disputed May election.
Government officials said one police officer was killed in the clashes and 18 wounded. They gave no further details.
Tuesday's violence broke out three days after Ethiopia's main opposition Coalition for Unity and Democracy (CUD) called for fresh protests over election results it says were rigged.
The appeal prompted the government to warn it would not accept any threat to security in the country of 77 million.
CUD officials said police arrested their leader Hailu Shawel and Berhanu Nega, a senior figure in the party, in the hours following Tuesday's disturbances.
Ambulances rushed casualties to two hospitals in Addis Ababa as police armoured personnel carriers patrolled the central Mercato market area.
The clashes saw demonstrators set up makeshift roadblocks of burning tyres and smash in the windscreens of several cars.
Many of the wounded said the police attacked first.
"I was on my way home when police attacked me with a stick. I was running for my life when I was shot in the arm," said Hunegnaw Teferi, 25, receiving treatment at St Paul's Hospital.
The authorities acknowledged people had been killed on Tuesday, saying those who were shot had tried to attack police.
"Those killed were those who attempted to assault police with machetes," Information Minister Berhanu Hailu told Reuters.
The disturbances were the first in Addis Ababa since post-election clashes killed 36 people in June, in the capital's worst violence in four years..
Political tensions in Ethiopia have intensified since the country's second real multi-party vote handed Prime Minister Meles Zenawi a third five-year term in power.
The euphoria generated by Ethiopia's most open electoral campaign quickly dissipated amid mounting opposition claims of intimidation by the ruling party, and an increasingly bitter war of words between the two sides.
Meles has repeatedly accused the opposition of plotting to incite violence and topple his government.
Once feted by Western leaders as part of a "new generation" of African leaders pursuing pluralism and clean government, Meles' democratic credentials have come under growing scrutiny over the election wrangling and his crackdown on civil unrest.
The political deadlock and reports of opposition arrests prompted the European Parliament last month to warn of possible cuts in development aid to donor-dependent Ethiopia.
The CUD had urged its members at the weekend to hold a stay-at-home strike beginning on Monday, attend peaceful demonstrations and stop listening to or watching state media.