"Today was the bloodiest day since the coup happened on the 1st of February."
Christine Schraner Burgener, The United Nation's special envoy for Myanmar, confirmed 38 people were killed in protests on Wednesday.
It was the country's most violent day since demonstrations broke out against last month's military coup.
Police and soldiers opened fire with live rounds in several towns and cities, witnesses said.
Four children were among those killed, according to aid agency Save the Children and local media reported hundreds have been arrested.
A 19-year-old woman, Kyal Sin, also known as 'Angel' was one of two shot in the second largest city Mandalay.
Images showed her in the protests wearing a T-shirt that read 'Everything will be Ok.'
One youth activist described in a message to Reuters that it was " horrific, it's a massacre."
Wednesday's bloodletting more than doubled the death toll since protests began.
A spokesman for the ruling military council did not respond to requests for comment.
In Washington, U.S. State Department spokesman Ned Price said the United States was "appalled" by the increase in violence.
"We call on all countries to speak with one voice to condemn brutal violence by the Burmese military against its own people and to promote accountability for the military's actions that have led to the life loss of life of so many people in Burma."
Meanwhile, the U.N. Security Council is due on Friday to hold a closed session on Myanmar.