Major cutbacks are planned at NHS England as part of government plans to “avoid duplication” with the Department of Health and Social Care.
It means around 6,500 jobs are at risk, about half the workforce at NHS England, with the aim of saving £175 million a year.
The news comes as it emerged three more NHS England board members will leave.
This follows recent announcements that chief executive Amanda Pritchard and medical director Sir Stephen Powis will quit.
NHS England was established in 2013 by former Tory health secretary Andrew Lansley to give it greater independence and autonomy.
Government sources have said the overall plan is to bring NHS England much closer to the Department and reallocate resources from central administration to regional health boards.
Sir Jim Mackey, the incoming interim chief executive due to replace Ms Pritchard from April, is set to oversee “a transition team” that will push through the “radical reduction and reshaping of the centre with the Department of Health”.
The plan will seek to reduce the duplication of jobs between the two organisations. Some of the job cuts could also be made within the DHSC.
NHS England chief financial officer Julian Kelly, chief operating officer Emily Lawson, and chief delivery officer Steve Russell collectively announced their decision to stand down at the end of March on Monday.
Health Secretary Wes Streeting said: “We are entering a period of critical transformation for our NHS. With a stronger relationship between the department and NHS England we will all work together to meet the scale of the challenge.”
Ms Pritchard added she believed it was the right time for “radical reform of the size and functions” of NHS England.
But she added: “I know this news will be very unsettling. The transition team will develop plans over the coming weeks and we know that colleagues will want this to be completed as soon as possible to provide future certainty.”