A pro-government mob broke in on Monday and injured a priest and a nun while attempting to dislodge activists demanding the release of political prisoners, church authorities in Managua said.
The Catholic Church has a powerful role in the country but President Daniel Ortega has accused bishops of supporting deadly anti-government protests that rocked the country last year.
The priest and nun were attacked when they attempted to block the group from taking control of the cathedral, according to an archdiocese statement.
Students shouting "Respect the Church" demonstrated at the Central American University in Managua on Tuesday, and threw water and dirt at security forces blocking the entrance.
They also demanded the release of 16 opposition activists, including Belgian-born student leader Amaya Coppens, who were arrested for trying to bring water to 11 female hunger strikers.
The UN human rights office voiced alarm at the harsh tactics used against the protesters.
"The government must end the persistent repression of dissent and the ongoing pattern of arbitrary arrests," UN rights office spokesman Rupert Colville told reporters in Geneva.
He also called on Managua to "refrain from criminalizing and attacking human rights defenders, political opponents and any other dissenting voices."
Nicaragua's political crisis erupted in April 2018, when protests mushroomed into a popular uprising against Ortega that was met with a brutal crackdown in which hundreds were killed.
Nine people began a hunger strike at the cathedral on Monday, four days after another group of 11 women began a similar protest at a church in the northern city of Masaya.
Both hunger strikes are part of an intensifying campaign for the release of 139 opposition protesters arrested during the 2018 demonstrations against Ortega.
But "violent" government supporters burst into the cathedral and police surrounded the church, according to the archdiocese.
The nine hunger strikers in the cathedral managed to take refuge in an annex where they spend the night, it said.
The Church of San Miguel in Masaya remains under siege by the police preventing any access to the 11 hunger strikers inside, leaving them without water or electricity, according to the opposition.
The incidents occurred after UNAB, and umbrella group of 92 opposition organizations, announced a new campaign to increase pressure on the government to release the prisoners in time for Christmas.
The opposition said it plans to hold a series of protests and simultaneous hunger strikes as well as a national strike to press for the release of political prisoners detained for taking part in anti-Ortega protests in April 2018.
The government has attributed the protests to a failed coup attempt and Ortega has accused Catholic bishops of being "coup plotters" for supporting the protesters.
State repression has been blamed for at least 325 deaths in last year's unrest, with an estimated 70,000 people forced to flee the country, according to the Inter-American Commission for Human Rights which has condemned the violence.
Opposition groups said at least 16 churches have been "besieged by police and government forces" in recent days to prevent them being used as protest venues.