Southampton chairman Nicola Cortese has handed in a written resignation according to reports.
The Italian is understood to have fallen out with the club's Swiss owner Katharina Liebherr over the future direction of the club.
It places into doubt the future of Southampton's highly-rated manager Mauricio Pochettino, who has said that he "would not understand staying in this role if Nicola was not here".
Cortese has been credited with helping the Saints rise from League One to an established Premier League club over the past four years. He also played a key part in the development of Southampton's new training ground which the team will begin using this summer.