48-year-old Ammar Gharsalla was staging a sit-in outside the Gafsa government office last week to highlight the region’s ongoing unemployment problem.
When three Tunisian government ministers refused to meet the group, Mr Gharsalla doused himself in petrol and set himself alight.
The father of three suffered third-degree burns and died in hospital on Monday.
It comes almost a year to the day that fruit-seller Mohamed Bouazizi died after setting himself on fire in January, 2011 to protest harassment by officials in the government of Zine el Abidine Ben Ali.
Bouazizi’s death sparked a revolt that toppled Ben Ali and sparked similar protests across the region, including the uprisings which led to the fall of Egyptian president Hosni Mubarak and Libya’s Muammar Gaddafi.