The Royal College of Nursing (RCN) suggested hard-working staff would feel that after a year spent in difficult conditions fighting coronavirus it was time to “move on”.
Ministers have been accused of snatching a 2.1 per cent pay rise, promised prior to the pandemic, from NHS workers.
The RCN is building a war chest ahead of possible strike action over the government’s 1 per cent pay offer in the coming weeks.
Ministers insist the rise is all the country’s coffers can afford after billions of pounds were spent fighting Covid-19.
But Patricia Marquis, the southeast regional director of the RCN, told Times Radio: "We know there are significant numbers who are planning to leave and this slap in the face from the government really has just reinforced their belief that they are not valued by either the government or perhaps some of the public in the way they would want to be.
"There is a real risk that, yes, we might get some new people in, but significant numbers of experienced, expert nurses will see the end of the pandemic [and think] that enough is enough, and ‘for all I have done for the last 30 years and certainly for the last year, I am still not valued and it is time to move on’."
She added that there had been 40,000 vacancies when the pandemic hit, and people were currently working to cover those roles.
But she added: "The last year has been as tough as anybody has had it for healthcare workers and those 40,000 vacancies will re-emerge as we come out of the pandemic over the next few months."
A former Conservative health minister has said now was the "wrong time" for pay restraint after NHS workers went "above and beyond" during the pandemic.
Dr Dan Poulter said it was valid for ministers to focus on the billions the government has been forced to borrow over the last year, but said: "A lot of health professionals in the early part of the pandemic were working without the right equipment to protect themselves, and many people have gone above and beyond the hours they are already paid for during the pandemic and have really pulled together in very difficult circumstances.”
He also called on ministers to accept whatever the independent health service pay review body recommends in terms of a salary increase.
Labour has argued the pay recommendation amounts to a "real terms cut" to wages as the independent Office for Budget Responsibility is predicting inflation will rise to 1.5 per cent over the coming year.
NHS Providers, the organisation which represents NHS trusts in England, also said it is "absolutely wrong" for ministers to renege on a pay rise that had already been budgeted for.
Simon Walsh, deputy chairman of the British Medical Association’s UK consultants committee, said the "derisory" recommendation "reflects that the government is really out of touch with the feeling of the public on this".
He added: "I hope [the government] realise that their policies are in danger of preventing the NHS from being able to recover from this pandemic and catch up with all the backlog of work."