The Egyptian Health Ministry said 72 people had been killed in the clashes between supporters of ousted President Mohamed Morsi and the interim government's security forces, The New York Times reported. Morsi's party, the Muslim Brotherhood, said it had counted 66 dead with 61 others "clinically dead," the newspaper said.
By the Brotherhood's count, 4,500 were injured, while the Health Ministry said only 177 were hurt, Ahram Online reported earlier.
Kerry said he spoke with interim Vice President Mohamed ElBaradei, interim Foreign Minister Nabil Fahmy and European Union High Representative Catherine Ashton, expressing the Obama administration's "deep concern about the bloodshed and violence in Cairo and Alexandria" he said had "claimed the lives of scores of Egyptian demonstrators and injured more than 1,000 people."
Kerry called the situation "a pivotal moment for Egypt."
"In this extremely volatile environment, Egyptian authorities have a moral and legal obligation to respect the right of peaceful assembly and freedom of expression," Kerry said. "Both are essential components of the inclusive democratic process they have publicly embraced.
"Violence not only further sets back the process of reconciliation and democratization in Egypt, but it will negatively impact regional stability.
"At this critical juncture, it is essential that the security forces and the interim government respect the right of peaceful protest, including the ongoing sit-in demonstrations."
Kerry said the United States urges an independent and impartial investigation into the latest violence and called on "leaders across the political spectrum to act immediately to help their country take a step back from the brink."
The violent confrontations occurred in Nasr City, a stronghold of Morsi and the Muslim Brotherhood. Interior Minister Mohammed Ibrahim early Saturday vowed to end a sit-in by Morsi supporters at the Raaba al-Adawiya mosque, saying it would be "brought to an end soon and in a legal manner," the BBC reported.
A Brotherhood supporter who gave his name as Karim told Ahram Online police had used both tear gas and live fire in Nasr City.
Police have denied using live fire on protesters.
The National Alliance to Support Legitimacy, a pro-Morsi coalition, issued a statement calling the deaths of protesters a "massacre."
Dr. Omar Amer, working at an improvised field hospital, told al-Jazeera the hospital had run out of supplies and medical workers.
Abdel-Fattah El-Sisi, the head of the Egyptian military, urged those who supported Morsi's departure to join demonstrations Friday in Cairo's Tahrir Square and across the country. He said the interim government needs to show it has a popular mandate.
The Brotherhood also called for demonstrations by its supporters.
The Times said some victims died of a single gunshot wound to the head.
"They had orders to shoot to kill," Brotherhood spokesman Gehad el-Haddad said.
The Times said Ibrahim denied his security forces were to blame for the deaths, saying his officers "have never and will never shoot a bullet on any Egyptian." The killing, he said, was the responsibility of the Brotherhood, whose members "preach and incite violence."
"We all hope and want the sit-ins to be broken up now, but blood is precious for us as well," he said. "Be sure that dispersing the sit-in with force will lead to losses."
In a post on Twitter, ElBaradei condemned the "excessive use of force."
The Times said the Pentagon released a statement saying Defense Secretary Chuck Hagel spoke by telephone with el-Sisi, urging restraint by Egyptian forces and for him to "take steps to prevent further bloodshed and loss of life."
Several protesters, including Mohamed Abdulhadi, said the demonstrators were unarmed and non-violent, the Times said.
An Interior Ministry video purported to show Morsi supporters firing birdshot at the police, throwing rocks and damaging property.
The Times said other witnesses said they saw rooftop snipers.
In Alexandria, at least seven people were killed and 100 wounded Friday, Ahram said.
On Friday, a court ordered Morsi held for 15 days for investigation of allegedly working with Hamas to engineer his escape from prison and with cooperating in the abduction and killing of police officers during the 2011 uprising against former Egyptian President Hosni Mubarak.