"We are appalled at the horrific deaths of at least 68 people in Venezuela after a fire swept through a police station jail," the UN human rights office said in a statement.
Wednesday's fire in Valencia, in Carabobo State, was thought to have been started deliberately during an attempted jailbreak.
It marks one of the worst tragedies in years in Venezuela's notoriously violent and overcrowded prison system.
"We urge the Venezuelan authorities to carry out a prompt, thorough and effective investigation to establish the cause of these deaths," the UN statement said.
It also called on Caracas to "provide reparations to the victims' families, and, where applicable, identify and bring those responsible to justice."
Venezuela's attorney general said Thursday that four prosecutors had been named to investigate the blaze, which in addition to detainees killed two women who were visiting the jail.
The rights office voiced concern at reports that "security forces had used tear gas to disperse relatives who had gathered in front of the police station... to demand information about their loved ones."
"We call on the authorities to respect the families' right to information and to peaceful assembly," it said.
Venezuela's prisons suffer from dire overcrowding and a shortage of basic supplies, struggling under the deepening economic crisis that is gripping the once-wealthy oil-producing country.
"States are guarantors of the lives and physical integrity of persons deprived of their liberty," the rights office pointed out.
It urged Venezuela to bring prison conditions in line with "international human rights norms and standards, including the prohibition of torture and cruel, inhuman or degrading treatment or punishment."
It also called on the country to allow for independent, international monitoring of its prisons.