"The deliberate starvation of people is unequivocally forbidden as a weapon of warfare. By extension, so are sieges, which deprive civilians of essential goods such as food," Zeid Ra'ad al-Hussein said.
In an address opening the UN Human Rights Council's main annual session, Zeid pointed to the desperate situation of the estimated 480,000 people "currently trapped in besieged towns and villages in Syria - and have been, in some cases for years."
Aid workers say several dozen people have died of starvation in Madaya alone. The town became a symbol of the plight of besieged Syrians after shocking images of starving residents spread last month.
But Zeid warned the situation could be far more dire.
"Thousands of people may have starved to death," he said.
His comments came as the UN was preparing to deliver aid to thousands of besieged civilians in Syria on Monday amid a fragile ceasefire.
The first major truce in five years, which after three days remained largely intact, was expected to allow aid workers to bring supplies to an additional 154,000 people living in besieged areas over the next five days.
But Zeid lamented that prior to the temporary cessation of hostilities that began on Saturday, human rights in the country had been "violated shockingly" for nearly five years.
"Neighbourhoods, schools and packed marketplaces have been hit by tens of thousands of air strikes, thousands of barrel bombs have been thrown out of helicopters onto streets and homes," he said of the conflict, which has cost more than 270,000 lives.
He also decried that some parties "are targeting medical units deliberately, or with reckless disregard," noting that at least 10 hospitals and other medical units have been damaged or destroyed since the beginning of the year alone.