Lethlean will leave the Saints in a decision painted as mutual by both parties, but coming amid speculation of tension between the administrator and coach Ross Lyon.
Lethlean was appointed as the club's chief executive in March 2022.
After being axed as the AFL's football operations manager in 2017 because of an inappropriate relationship with a younger female staffer, he joined the Saints as football manager the following year.
Lethlean then served as chief operating officer before taking the CEO job, which president Andrew Bassat says now requires a different skill-set.
Bassat says the club's board and Lethlean have decided the requirements of the CEO have shifted.
"The club has undergone significant changes as a result of the 2022 football program review," Bassat said in a statement on Thursday.
"(It) highlighted the need to elevate our football department and place football at the heart of everything we do, which we hope will see St Kilda competing for premierships before too long."Simon and the board share the view that a new CEO would be best placed to take the club forward."
In mid-2022, Lethlean oversaw the re-signing of Brett Ratten as coach, only for the end-of-season review to sack Ratten and appoint Lyon.
Lethlean said he had "loved every role" at the Saints.
"The club has a new coach and a new strategy and I have agreed with the president that it is time for the club to seek a new CEO," he said in a statement.
13°C