As a nationwide state of emergency was declared, clashes between police and protesters demanding reinstatement of ousted President Mohamed Morsi left at least 235 civilians and 43 police officers dead, the BBC reported. The Muslim Brotherhood, which backed Morsi, put the death toll at more than 2,000.
Egyptian police said they've taken control of the protesters' camps and arrested key Brotherhood leaders.
Morsi was deposed by the military July 3 and an interim government was installed.
Interim Prime Minister Hazem Beblawi said in a televised address he regretted the loss of life and police had been told not to use weapons in dispersing the protests, the BBC reported.
An 11 p.m. to 6 a.m. curfew was in effect in Cairo.
Kerry urged restraint.
"Today's events are deplorable, and they run counter to Egyptian aspirations for peace, inclusion, and genuine democracy," Kerry said during a media availability in Washington.
"Egyptians inside and outside of the government need to take a step back. They need to calm the situation and avoid further loss of life. We also strongly oppose a return to a state of emergency law, and we call on the government to respect basic human rights, including freedom of peaceful assembly and due process under the law. And we believe that the state of emergency should end as soon as possible."
Egyptian Vice President for Foreign Affairs Mohamed ElBaradei resigned in protest in a letter to interim President Adly Mansour, Ahram Online reported.
Sources told the website police and the military leadership made the decision to disperse protester sit-ins forcefully, without notifying Beblawi or the vice president for external relations.
In the letter, ElBaradei told Mansour: "As you know, I saw that there were peaceful ways to end this clash in society, there were proposed and acceptable solutions for beginnings that would take us to national consensus. It has become difficult for me to continue bearing responsibility for decisions that I do not agree with and whose consequences I fear. I cannot bear the responsibility for one drop of blood."
Ahram Online said two other ministers also were expected to resign.
Mansour declared a monthlong state of emergency across the country Wednesday even as the Muslim Brotherhood vowed to keep on with its sit-ins.
Egyptian police used armored vehicles and bulldozers to clear two Cairo camps, witnesses said.
"We will not accept the rule of coup perpetrators who open fire at protesters in squares and on the street," said Hamza Zawba, a spokesman for the Brotherhood's Freedom and Justice party.
He said protesters would face police weapons "with bare chests."
State TV showed Egyptian security forces pushing into the larger of the two encampments around the Rabaa al-Adawiya mosque in the northeastern suburb of Nasr City.
The smaller encampment was at Nahda Square near Cairo University.
Rail service in and out of Cairo was reported suspended to prevent pro-Morsi demonstrators from regrouping or summoning reinforcements, The New York Times said.
A spokesman for the European Union said reports of protesters being killed were "extremely worrying" and called on Egyptian authorities to use restraint.
The German foreign minister said all sides should "return immediately to negotiations and avert an escalation of violence," Ahram Online reported.