Ahmed Douma has been jailed since 2013 on charges of clashing with security forces during a protest in Cairo two years earlier.
He received a 25-year prison sentence in 2015, but a court overturned the ruling in 2017 and ordered a retrial.
In January last year, Douma was sentenced to 15 years in prison and fined six million Egyptian pounds ($372,000).
Saturday's verdict by the court of cassation upheld that sentence, which "is now final and cannot be appealed", the judicial source told AFP.
Douma was a leading activist in the 2011 uprising that toppled former president Hosni Mubarak.
He was arrested in a crackdown following the 2013 military ouster of Mubarak's successor, Mohamed Morsi, led by now-President Abdel Fattah al-Sisi.
Thousands of Morsi's supporters as well as secular activists, lawyers and academics have been swept up in the crackdown.