A general strike and more protests expected today as demonstrations demanding President Ortega's resignation leave over 200 dead in the country's bloodiest protests since civil war ended in 1990.
Four police officers and a protester were killed on Thursday in a confrontation in Nicaragua, where violent unrest has left over 260 people dead in three months amid anti-government demonstrations.
The rise in death toll comes even before a fresh wave of protests and strikes are expected to start on Friday.
"Five people died in a confrontation in Morrito, of whom four were police officers and one a protestor," Vilma Nunez, president of the Nicaraguan Center of Human Rights (CENIDH), said.
More than two months of demonstrations over demands for the resignation of Nicaraguan President Daniel Ortega amid the bloodiest protests in the Central American nation since its civil war ended in 1990.
Thursday's face-off took place where a march passed near a police command in Morrito in the Rio San Juan department in southeastern Nicaragua, during a day of demonstrations in the crisis-stricken country called by the opposition Civic Alliance for Justice and Democracy.
Movement leader Francisca Ramirez, said the protesters, some of whom were armed, were "attacked by agents and paramilitaries," and responded with gunfire.
The police have not yet offered their version of events, but have previously accused "criminal gangs" of carrying out murders, robberies and abductions.
Morrito, a town of 6,000 people, is home to many farmers who are armed to protect their land. It is located 230 kilometres (140 miles) southwest of the capital Managua, on the route of a proposed intercoastal canal opposed by locals.
United Nations Secretary-General Antonio Guterres expressed deep concerns about intensifying violence in Nicaragua in protests against Ortega, his spokesman said in a statement on Wednesday.
Protests erupted in Nicaragua on April 18, initially against now-scrapped pension reform. However, they have since boiled over into demands for Ortega, a former left-wing guerrilla leader whose second stint in office began in 2007, to step down.
His detractors accuse him and his wife Vice President Rosario Murillo of establishing a brutal dictatorship.