Mr Sisi served as Mr Mubaraks military intelligence chief and led the militarys overthrow of his democratically elected successor, Mohammed Morsi, in 2013.
In all, more than 800 people are believed to have been killed as security forces sought to stop protests in Cairo, Alexandria, Suez and other cities around Egypt during the 18-day uprising that forced Mr Mubarak to resign after 30 years in power.
Image copyrightAPImage captionSupporters celebrated Mubaraks acquittal outside the hospital where he is confined
He denied ordering the killing of protesters and insisted that history would judge him as a patriot who served his country selflessly.
Mr Mubaraks first retrial was ordered in 2013. A judge dropped the charge altogether the following year, but the Court of Cassation ordered a second retrial.
Former Interior Minister Habib al-Adly and four of his aides were also acquitted of the same charge on Thursday.
The Court of Cassation also rejected demands by lawyers of the protesters families to pursue civil suits against Mr Mubarak.