Front-runner for the White House Hillary Clinton has become the latest heavyweight American politician to wade into the referendum campaign and warn against a Brexit vote.
Ms Clinton, who is almost certain to clinch the Democratic Party's presidential nomination, and leads in most polls for the November election to succeed Barack Obama, has made it clear she thinks it would be a mistake for the UK to go it alone.
The former secretary of state's senior policy adviser, Jake Sullivan, told The Observer: "Hillary Clinton believes that transatlantic cooperation is essential, and that cooperation is strongest when Europe is united. She has always valued a strong United Kingdom in a strong EU. And she values a strong British voice in the EU."
The latest foreign intervention came as Leave campaigners launched a furious backlash against Mr Obama, branding him an irrelevant "lame duck" after the US president warned Britain would be at "the back of the queue" for American trade deals if it backed Brexit.
Justice Minister Dominic Raab led the personalised attacks against Mr Obama as the Leave campaign tried to shift the emphasis of the campaign to immigration.
He said: "This is really about a lame duck US president about to move off the stage doing an old British friend a favour.
"I have got no doubt that future US trade negotiators are going to look to other opportunities - I think the British will be first in the queue, not at the back of the queue."
The attack came after Mr Obama set out in stark terms that Britain would not be able to strike a free trade deal with the US "any time soon" if it leaves the European Union (EU) because Washington's focus would be on reaching agreement with Brussels.
Former Tory leader and ex-work and pensions secretary Iain Duncan Smith moved to switch attention to immigration as he insisted the living wage would provoke a "stampede" to Britain from poorer EU nations.
He wrote in The Daily Mail: "I cheered the introduction of the national living wage, but when take-home pay in Britain is already more than five times higher than in the poorest EU countries, such a jump in wages will surely lead to another stampede to our borders.
"To make the living wage work for British people, we need to be able to control the number of people coming in."
Ukip leader Nigel Farage also savaged Mr Obama's trade deal remarks, insisting the president did not know what he was talking about and was being manipulated by Number 10.
"He said Britain would be at the back of the queue, no American would ever say 'back of the queue', Americans don't use the word 'queue', Americans use the word 'line'," Mr Farage told BBC Radio Four's Any Questions.
"Therefore, what Obama said when he said we would be at the back of the queue, he was doing the bidding of Cameron, and Number 10, and doing his best to talk down Britain, and I think that's shameful."
Tory former defence secretary Liam Fox said Mr Obama's views would be irrelevant after the looming US presidential election.
"We have a referendum at the end of June, presidential elections are in November, so whoever it is that will be at the helm of the United States won't be Barack Obama. So, to an extent, whatever he says today is largely irrelevant," he told BBC Two's Newsnight.
"It will be the next president, and the next congress, who will be in charge of any trade arrangements."
Leave backer and former foreign secretary Lord Owen told BBC Radio 4's Today programme Mr Obama's trade embarks had been "crafted" in Downing Street.
London mayor Boris Johnson stood by his remarks that Mr Obama;s comments were "perverse".
At a joint press conference with Prime Minister David Cameron, the president stressed the referendum was a "decision for the people of the United Kingdom" and he was "not coming here to fix any votes".
He added: "I think it's fair to say that maybe some point down the line there might be a UK-US trade agreement, but it's not going to happen any time soon because our focus is in negotiating with a big bloc, the European Union, to get a trade agreement done.
"The UK is going to be in the back of the queue."
Mr Cameron said the referendum was the "sovereign choice of the British people" but added: "As we make that choice, it surely makes sense to listen to what our friends think, to listen to their opinion, to listen to their views, and that's what Barack has been talking about."