"The presidency of the Syrian Arab Republic mourns the death of the adviser Luna al-Shibl, who passed away today after a serious car accident", it said in a statement.
"She served in recent years as a director of the political and media office of the presidency and then as a special adviser to the presidency," it added.
State media reported on Tuesday that she had suffered a "cerebral haemorrhage" which required emergency surgery after her car "veered off the road" .
The 48-year-old rose to prominence for quitting a prestigious journalism career at Qatar-based broadcaster Al Jazeera to become Assad's media adviser at a time when Damascus was cracking down on peaceful protesters in 2011, triggering Syria's ongoing civil war.
But her role expanded well beyond communications, carving out a place within Assad's inner circle as she accompanied him to high-level meetings in Syria and on his rare visits abroad.
She played an important role during the most intense years of the civil war and was part of the delegation to ultimately doomed peace talks in 2014.
Britain-based war monitor, the Syrian Observatory for Human Rights, reported earlier this week that she had fallen out of official favour in recent months and her brother had been arrested.
"There was growing dissatisfaction with her within the regime," said Observatory director Rami Abdulrahman.
"Accusations surfaced that she leaked minutes of closed meetings between Assad and Iranian officials," Abdulrahman added.
Syrian intelligence arrested her brother "on charges of communicating with a party hostile to Syria" after Israel struck the Iranian consulate in Damascus in April, the monitor said.
In 2020, Washington sanctioned Shibl and her husband Ammar Saati, with the US Treasury saying at the time that "she has been instrumental in developing Assad's false narrative that he maintains control of the country and that the Syrian people flourish under his leadership".
