A nursing union has warned that the NHS would be put "under real strain" if thousands of jobs are cut.
At least 5,600 posts could be in danger as the NHS in England tries to drive down its spending, according to data from 26 NHS trusts.
Howard Catton, Head of Policy at the Royal College of Nursing, warned that the figure could increase to more than 36,000 in a "worst case scenario" and if the data are extrapolated across all hospital trusts.
He said that the loss of posts - including redundancies and staff not being replaced if they leave or retire - could take place over the next three years.
The NHS may have to implement job losses in all areas of the NHS, including nursing posts.
As part of a bid to save money across the board, the NHS has been asked to find between £15 and £20bn in efficiency savings over the next three years.
Mr Catton said a number of trusts "were deliberately holding back in being clear" on where efficiency savings would strike.
Dr Peter Carter, General Secretary of the Royal College of Nursing (RCN), said the drive to find up to £20bn could lead to "less staff being asked to do more" and longer waiting times for patients.
Dr Carter said he had not seen an analysis of how the £20bn figure had been arrived at, but politicians could not claim that sort of cash could be removed with no impact on the front line.
He said it was "disingenuous" to suggest you could remove £20bn from the £100bn NHS budget and "nothing changes".
A Department of Health spokeswoman said: "In delivering efficiency improvements, service change proposals must demonstrate a strong clinical case for change, promoting better outcomes for patients."
"It seems that job cuts are inevitable in these dire economic times, I am also very concerned by the government's drive to coerce PCTs to become social enterprises, effectively removing community care from the NHS structure. All this activity around the time of the general election, so this major development is not picked up by the national press until it is too late" - Francine Nutt, Shropshire