Steve Barclay has been told to "stop the spin" and "start to speak" with nurses in a bid to avert the first ever nationwide nurses' strike.
The General Secretary of the Royal College of Nursing Pat Cullen accused the Health Secretary of having "chosen strikes over speaking to me".
Labour leader Keir Starmer also pinned the blame for the industrial action on ministers - branding it a "badge of shame" for the Government.
Neither Labour’s leader nor the Prime Minister said they backed the RCN’s call for a pay award of 5% above inflation as cost of living pressures spiral.
The Retail Prices Index measure of inflation currently stands at 14.2%.
Rishi Sunak claimed to have "enormous respect" for nurses - but said a 19% pay rise is "obviously unaffordable".
The Prime Minister told broadcasters: "I have enormous respect and gratitude to our nurses as everyone does for the incredible job they do.
"And I know things are difficult right now for everyone because of what's happening with inflation.
"And that's why our plans that we outlined last week will get a grip of inflation and bring it down. That's really important.
"And in the meantime, what the unions are asking for, I think, is a 19% pay rise.
“And I think most people watching will recognise that that's obviously unaffordable, and that's why I'm pleased that the Health Secretary is sitting down, talking to the union, and hopefully we can find a way through this."
Asked in a broadcast interview today, Keir Starmer swerved saying if he would support the RCN's pay demands if he was PM.
But he said unlike the Tories, he would "get round the table" and have the discussion about pay.
Highlighting his plan to end non-dom tax breaks and use the funds to train up to 15,000 new doctors, he added: “It is about pay but it is also about staffing.
“Because talk to anybody in the NHS - my wife works in the NHS - and they will tell you they are under so much strain when it comes to staffing.”
It came after the RCN union announced the dates for the first strike in its 106-year history, with members set to stage a walkout on December 15 and 20.
Services deemed "life-preserving" and "emergency-type care" will continue on strike days, nursing chief Pat Cullen said.
But she declined to give exact detail about which departments would remain staffed when colleagues stage a walk-out.
A detailed list of services exempt from industrial action will be released "very soon", Ms Cullen told the BBC.
The Health Secretary Steve Barclay insisted his door remains open to discuss with the RCN “ways we can improve nurses' working lives". He added: "Our priority is keeping patients safe.”
No10 also claimed it was not correct that ministers had declined formal negotiations, insisting they were" engaging with unions, including the RCN".
"However, NHS nurses' pay is an independent process. And the Government accepted the recommendations in full."
The charity director of Age UK Caroline Abrahams said it is now the "responsibility of all parties to get round the table and do whatever it takes to resolve this dispute, so they never actually take place".
She added: “Nurses are the backbone of the NHS and do one of the most important jobs in our society.
"They need rewarding accordingly, and they need to be cared for too, especially after all they experienced during the pandemic."
