The "Battle of the Camel," named after Mubarak supporters mounted on camels and horses who charged protesters, was seen as pivotal in drawing more crowds to join the anti-regime rallies.
Today's court's decision will come as a blow to Islamist President Mohamed Mursi, who pledged to deliver justice for early victims of the 2011 uprising when he was elected in June.
"The Court of Cassation... Issued a final ruling in support of the Cairo criminal court's decision to acquit all defendants in the case of protester killings on February 2 and 3 (2011)," the official MENA news agency reported.
Mubarak was eventually ousted on February 11 after nearly three weeks of mass protests in which 846 people were killed and more than 6,000 injured.
Mubarak himself was sentenced to life in prison over the protesters' deaths, but a court overturned the verdict and he will face a new trial on Saturday.
In other trials, policemen accused of killing protesters have either been acquitted or received light sentences.
He has also been accused of interfering with the judiciary, notably after the controversial sacking of the Mubarak-appointed state prosecutor, and could face unrest within the police if he pursued cases against them.
