Reyes, who shot to fame at Sevilla before a switch to Arsenal followed by spells at Real and Atletico Madrid, was on the books with second tier Spanish club Extremadura.
"We couldn't be confirming worse news. Beloved Sevilla star Jose Antonio Reyes has died in a traffic collision. Rest in peace," Sevilla, where he spent two four-year spells, said on Twitter.
Current club second tier Extremadura also went on to announce the news.
"With broken hearts we announce the news of our player Jose Antonio Reyes' death in a car crash and we ask for you to pray for his soul," the club said.