Former top City regulator Sir Hector Sants has resigned from his post in charge of compliance at Barclays after being signed off work last month with stress and exhaustion.
Barclays said Sir Hector, who was on sick leave until the end of the year, stepped down after deciding he would not be able to return to work in the near term.
His departure comes less than a year after he took on the role of head of compliance, government and regulatory relations at the scandal-hit bank - a post he took on after a gruelling five years at the helm of the Financial Services Authority (FSA) in the run up to and throughout the financial crisis.
Antony Jenkins, group chief executive at Barclays, said: " Although only with us for 10 months, he has made significant progress towards creating a world class compliance function at Barclays and in improving our relationships with regulators and governments.
"I know my colleagues will join me in expressing our appreciation to Hector, as well as wishing him a speedy recovery."
Sir Hector's health woes come after Lloyds Banking Group chief executive Antonio Horta-Osorio also took two months off at the end of 2011 due to sleep deprivation and exhaustion.
Barclays has launched the search for a permanent replacement for Sir Hector, with Allen Meyer, head of compliance, corporate and investment banking taking on the job on an interim basis.
The bank is also looking for a chief operations and technology officer following the resignation of Shaygan Kheradpir to become chief executive of a company based in the United States.
The compliance role left by Sir Hector is seen as a crucial part of the overhaul being led by Mr Jenkins.
His appointment marked the first time the bank brought its compliance operations under the control of one person and followed its £290 million fine last year for attempting to manipulate the Libor interbank lending rate - a scandal that threw the bank into turmoil and claimed the scalp of its former boss Bob Diamond.
The job involves liaising with regulators and government and to ensure rules are followed at the bank, with responsibility for monitoring questionable trading.
Sir Hector was knighted in the Queen's New Year Honours for services to financial regulation after overseeing sweeping reforms following the nationalisation of Northern Rock and bailout of major banks.
But the knighthood was also seen as a controversial decision, as it was Sir Hector who led the organisation accused by MPs of being "asleep at the wheel" in the run up to the collapse of Northern Rock.
The Oxford graduate, who is married with three children, started his career in 1977 with Phillips & Drew stockbrokers, which was taken over by Swiss banking giant UBS in 1985.
He remained with UBS until 1998 when he joined Donaldson, Lufkin and Jenrette International Securities and then later joined Credit Suisse in 2000.
He became FSA chief executive in 2007.