"We do have a principled position in the United Nations that no amnesties should be considered for those suspected of having committed crimes against humanity or war crimes," UN rights chief Zeid Ra'ad al-Hussein told reporters in Geneva.
His comments came as indirect UN-brokered talks between Syria's warring parties, which had been scheduled to start last week, continued to struggle to get off the ground.
"Naturally after five years of this most gruesome spectacle of seeing the Syrian public subjected to public executions we hope and pray that the talks being mediated by (UN Syria envoy) Staffan de Mistura will lead to the end of all of these horrific abuses, human rights abuses, violations of international humanitarian law," he said.
He condemned the tragic scenes unfolding in the besieged city of Madaya, where 46 people have starved to death since December, according to the Doctors Without Borders (MSF) charity, which warned Saturday dozens more were on the verge of death.
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He also said that his office estimates that "tens of thousands of persons (in Syria) are currently being held under arbitrary detention."
"Clearly they need to be released."
More than a quarter of a million people have been killed since the conflict erupted in 2011, and half the country's population has been forced to flee their homes.
While urging a swift end to Syria's war, Zeid said negotiations needed to steer clear of offering amnesties for the worst of the crimes committed.
"In the case of Syria, we are here to remind everyone that where allegations reach the threshold of war crimes or crimes against humanity, amnesties are not permissible.