Former Labour Foreign Secretary Lord Owen says leaving the EU is necessary to protect the NHS from interference and stop the spread of market forces.
The peer, who backed Britain's membership in the 1975 referendum, said he had been wrong to think the "common market" would "leave the NHS alone".
He warned a planned trade deal between the EU and US would harm the NHS.
But Labour's Rachel Reeves said EU membership had helped the NHS fund research and recruit skilled workers.
And she suggested the Transatlantic Trade and Investment Partnership (TTIP) he is concerned about was being "manipulated" by Leave backers, many of whom did not support the NHS.
The NHS has become the latest battleground for arguments over whether the UK is better off inside or outside the EU ahead of the referendum on 23 June.
Earlier this week, four former Labour health secretaries said a vote to leave the EU would seriously undermine the NHS and its founding principle of care free at the point of use.
The Leave campaign retaliated with claims about the cost to the taxpayer of treating EU nationals using the NHS.
Now Lord Owen - a former GP who has campaigned against government health reforms in recent years - has said the NHS needs to be "protected" from EU interference, which he believes its threatening its heritage and independence.
In a speech in London in support of the Vote Leave campaign group, Lord Owen - who served as Labour foreign secretary in the late 1970s before defecting to the SDP and is now a crossbench peer - said the dream of European co-operation once supported by many on the centre-left of politics had turned sour.
In the past 20 years, he said the EU had "crept into every nook and cranny" of British life, including the NHS, and had to stop.
The European Commission, he said, had become "obsessed with proposing market solutions to social policy" and, in respect of health legislation emanating from Brussels, patients were being treated as consumers.
"In truth, since 2002 the Labour government, the coalition government and now the Conservative government have accepted an EU market in health," he said.
He said the application of EU competition law to the NHS would be exacerbated by the passing of TTIP, a set of free trade and regulatory agreements which he said had "no regard for the social purpose of healthcare" and would erode member states control over healthcare policy and spending.
Leaving the EU would prevent any future UK government from ratifying TTIP, he said. "We all need to respect and value, whatever political parties we support, those elements which bind the citizens of the UK together and the NHS is one of those.
"Now is the time to take back control from the EU and protect our NHS for future generations."
Several trade unions, while backing EU membership, are opposed to TTIP, saying it would allow private firms running NHS services to sue the government if it chose to return the services to the public sector - a claim rejected by the government.
Unison, the main union for NHS workers, say it is a threat to public services and should be rejected unless changes are made.
Ms Reeves, who backs continued EU membership, said she understood concerns on the left that TTIP would be a "Trojan Horse for further privatisation of the health service" but believed they were unfounded.
In an article for Labour List, the former Labour frontbencher said the issue was being exploited by those backing EU exit "many of them right-wingers with no love for the NHS".
"Let me be clear. I would not support TTIP if I believed in any way that it would allow American health providers to sue our government into breaking open the NHS, as some claim it would.
"Thankfully, anyone who studies both the detail and the political intention of this deal can see that it poses no threat at all to our health service.
"What it will do is open up the American market to British companies, creating opportunities for business that will boost jobs and growth here at home."
At a time of acute challenge for the NHS, she said the "last thing" it needed was the "shock" of EU exit.
"The EU has made the NHS stronger, providing it with research funding, skilled workers and the economic stability needed to plan future spending. Exit would put all this in peril."