Susan Elizabeth, the chief executive of the Camelot Foundation, has resigned after five years leading the grant-giver.
Elizabeth, who has worked in the voluntary sector for more than 20 years, was previously director of grants at the King's Fund and deputy director of the National Council for One Parent Families.
A statement from the foundation's trustees said that Elizabeth had made a "tremendous contribution" to the development of the organisation.
The trustees did not give a reason for her sudden departure, but a foundation spokeswoman said that Elizabeth had been unwell for some time.
"The trustees and staff of the foundation extend their thanks to Susan and wish her well in the future," the statement concluded.
Samantha Hyde, the assistant director, has become acting chief executive.