These deaths, confirmed by the local Red Cross, are the latest in a wave of protests against social security reforms that have rocked this Central American nation.
Protesters opposed to President Daniel Ortega's government clashed with riot police and Sandinista Youth groups in cities across Nicaragua Saturday, with demonstrators burning tires and setting up barricades in violence that left two people dead and dozens injured.
Videos released by protesters on social media showed two people who had apparently been shot in the head during demonstrations in Masaya, a town 20 miles (30 kilometers) southeast of the capital, Managua. The local Red Cross confirmed two deaths in a statement.
In a live transmission on social media a young man is seen crying and carrying an apparently lifeless body, saying: "Crazy, they shot him in the head, he fell and they kicked him on the ground! He was a child."
Besides Masaya, protests were also reported in Chinandega, Granada, Leon, Managua, Masaya and Rivas in the Pacific region, as well as in Esteli and Matagalpa in the north.
In Masaya, the house of the former mayor Orlando Noguera was set alight by protesters.
The demonstrations began in April as protests against social security reforms but have expanded into calls for the Sandinista president to step down.
Ortega addressed Nicaraguans in a brief message Saturday, describing events in Masaya as painful and calling for an end to the violence.
"Peace is the path and the only door to coexistence and respect for the tranquility and security of us all," he said.
Government spokeswoman and Vice President Rosario Murillo said the government has agreed to start a national dialogue mediated by the Roman Catholic Church as soon as possible.
Before Saturday's deaths and several other deaths reported on Thursday, a human rights group estimated 63 people had been killed.