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Saturday's sentencing, which included jail terms for more than 600 others, concluded a mass trial of people accused of murder and inciting violence during the pro-Muslim Brotherhood protest at Rabaa Adawiya square in Cairo.
The decision can be appealed within 60 days.
Rabaa square was the single most deadly incident in unrest which followed the 2011 popular uprising that toppled Egypt's longtime leader Hosni Mubarak.
It occurred weeks after the military ousted Egypt's first freely elected head of state, Islamist president Mohamed Mursi.
The government says many protesters were armed and that eight members of the security forces were killed.
Rights groups say more than 800 protesters died. Amnesty International condemned Saturday's decision, calling the trial "disgraceful".
Those sentenced to jail included a US citizen, Moustafa Kassem, rights group Pretrial Rights International said. Washington is Cairo's closest Western ally and one of its top aid donors.
President Abdel Fattah al-Sisi on Saturday met US Central Command chief General Joseph Votel as the two countries launched a joint military exercise off Egypt's Mediterranean coast.
In Saturday's hearing at the vast Tora prison complex south of Cairo, a criminal court sentenced to death by hanging several prominent Islamists including senior Brotherhood leaders al-Erian and Beltagi and preacher Safwat Higazi.
Muslim Brotherhood spiritual leader Mohamed Badie and dozens more were given life sentences, judicial sources said. Others received jail sentences ranging from five to 15 years.
Cases were dropped against five people who died while in prison, judicial sources said.
Following weeks of protests against the ouster of Islamist President Mursi by the military, which at the time was led by current president Sisi, security forces violently broke up the Rabaa square demonstration.
They arrested hundreds of people who were charged with inciting violence, murder and organising illegal protests.
'MOCKERY OF JUSTICE'
Rights groups have criticised the trial for including many peaceful protesters and journalists.
An award-winning photographer who covered the protests, Mahmoud Abu Zeid, was sentenced to five years in jail, but would soon be released because his five years in detention during the trial are counted towards the sentence, judicial sources said.
Abu Zeid, also known as Shawkan, was awarded a UN World Press Freedom Prize this year. He was charged with belonging to a banned group and possessing firearms.
"We condemn today's verdict in the strongest terms," Amnesty International said in a statement. "The fact that not a single police officer has been brought to account ... shows what a mockery of justice this trial was."
Since Sisi was elected president in 2014, authorities have justified a crackdown on dissent and freedoms as being directed at militants and saboteurs trying to undermine the state.
Death sentences have been handed down to hundreds of his political opponents on charges such as belonging to an illegal organization or planning to carry out an attack. Often the sentences are not carried out, but rights groups say hangings have increased in recent years, with dozens taking place each year.
For executions to take place, Sisi must issue a final approval.
Supporters say a security crackdown is needed to stabilise Egypt, which still faces an Islamist insurgency in the Sinai Peninsula and is reeling financially from years of unrest.
Critics say the erosion of freedoms and silencing of political opponents is the worst Egypt has seen in its modern history.