UN High Commissioner for Human Rights Zeid Ra'ad Al Hussein said he was "deeply disturbed" by the deaths in clashes that have raged in Egypt since Friday.
He demanded in a statement that Cairo "take urgent measures to bring an end to the excessive use of force by security personnel."
Zeid's comments came after 20 people were killed Sunday when protesters clashed with security forces after Islamists called for rallies against President Abdel Fattah al-Sisi's government as Egypt marked the fourth anniversary of the toppling of ex-strongman Hosni Mubarak.
Sunday's death toll marked the highest for a single day since Sisi came to office after a landslide election victory last May.
"Hundreds of people have died during protests against successive governments since January 2011, and there has been very little in the way of accountability," Zeid said.
"The lack of justice for past excesses by security forces simply encourages them to continue on the same path," he warned, pointing out that this was "leading to more deaths and injuries, as we have seen in recent days."
At least 97 people had also reportedly been injured in clashes in a range of cities, including Cairo, the statement said.
"I have in the past urged the Egyptian authorities to take urgent measures to ensure that any excessive use of force by security personnel is promptly investigated, alleged perpetrators are put on trial and victims have access to justice and compensation," Zeid said.
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