Switzerland's supreme court said it was clear that 41-year-old Hafez Makhlouf and his 80-year-old father, Mohamad Makhlouf — Assad's cousin and uncle, respectively — played key roles in backing the Syrian regime.
The two men took court action after being placed on a sanctions list by the Swiss in 2011, the year a crackdown on anti-Assad protests heralded the start of Syria's brutal civil war.
Shortly before his assets were frozen, Makhlouf senior tried unsuccessfully to transfer $10 million (7.5 million euros) to his wife from his bank account at the Geneva branch of British bank HSBC.
His son, meanwhile, is widely seen as a leading backer of the tough line taken against the rebels and their supporters by government forces, whose human rights abuses have sparked condemnation from much of the international community amid a conflict estimated to have killed at least 94,000 people.
Despite having failed to win their case in the Swiss justice system, the two men can still turn to the European Court of Human Rights for a final legal attack.