"There must be an independent, impartial, effective and credible investigation of the conduct of the security forces. Anyone found guilty of wrongdoing should be held to account," Pillay said in a statement.
More than 500 people, according to government figures, were killed in yesterday's assaults on two Cairo protest camps of supporters of ousted Islamist president Mohammed Morsi in the country's worst violence in decades.
The Muslim Brotherhood has put the death toll at more than 2,000.
"The number of people killed or injured, even according to the government's figures, point to an excessive, even extreme use of force against demonstrators," Pillay said.
"I deplore the loss of life and call on all in Egypt to seek a way out of the violence," she said.
Pillay urged the Egyptian authorities and security forces "to act with the utmost restraint," saying they were "bound by the rule of law and must act with full respect for human rights."
The UN rights chief also said she was deeply worried by reports of government opponents attacking public buildings and religious sites, insisting that those responsible should be brought to justice.
Pillay also said the month-long state of emergency imposed by the authorities must conform with Egypt's obligations under international law.
"Everyone deprived of their liberty must be treated humanely and afforded all the judicial guarantees under international law," she said.