A general strike called by ethnic groups a day after police fire killed at least three protesters shut down markets, schools and transport in much of southern Nepal on Tuesday.
Police had opened fire Monday on protesters attempting to disrupt a political rally, killing at least three and wounding dozens in southern Nepal, which has been hit by violent protests over the last year.
On Tuesday, protesters blocked main highways and towns to enforce the general strike.
They attacked several government offices and vandalized a vehicle from the National Human Rights Commission, which had a team monitoring the situation. There were minor clashes between police and the protesters, but no one was hurt.
The commission said it was probing the police firing and monitoring the fresh violence in the area.
Home Ministry official Bal Krishna Panthi said police first tried to disperse the protesters with bamboo batons and tear gas before firing their guns.
He said three people were fatally shot and 33 police officers injured in the clash. He could not say how many protesters were hurt.
Police stepped up security Tuesday in southern towns and increased patrols on highways, which were mostly deserted because of the general strike.
The U.S. Embassy in Kathmandu issued a statement saying it was deeply concerned at signs of rising volatility in some areas of Nepal.
The violence Monday broke out after the Communist Party of Nepal (United Marxist Leninist) attempted to hold a rally in Rajbiraj town, 400 kilometers (250 miles) southwest of Kathmandu. Ethnic Madhesi groups oppose the party and have vowed to stop its rallies.
The Communist Party of Nepal was in power and its leader, Khadga Prasad Oli, was prime minister when the Madhesis held protests between August 2015 and February 2016 after Oli rejected their demands for changes to a new constitution that would give the ethnic group more territory in proposed federal states.
The protests shut down southern towns for months, blocking the border with India and stopping the supply of fuel and medicine.
The protests eventually fizzled out and a new administration that took power in August 2016 promised to address the demands by the Madhesis.
The protests have been held in southern towns since Saturday and come ahead of district and municipal elections set for May.