Donald Trump says Theresa May's Brexit agreement "sounds like a great deal" for the EU but may hinder trade between the UK and US.
Speaking to reporters before a trip to Mississippi, the president said the deal Mrs May secured with Brussels may not be good for trade.
"I think we have to take a look at seriously whether or not the UK is allowed to trade because you know right now, if you look at the deal they may not be able to trade with us," he said.
"That wouldn't be a good thing. I don't think they meant that, I don't think the prime minister meant that and hopefully she'll be able to do something about that but right now as the deal stands they may not be able to trade with the US and I don't think they want that at all, that would be a very big negative for the deal."
Responding to Mr Trump's comments, a spokeswoman for the prime minister said that under the existing Brexit agreement the UK will be able to sign trade deals.
She added that the government had already been "laying the groundwork" for an "ambitious" trade agreement with the US.
Mrs May has spent the last 20 months negotiating an exit agreement with the EU and now faces a fight to get her deal through the House of Commons.
A meaningful vote is set to take place on 11 December.
Labour MP Tulip Siddiq, a supporter of the Best for Britain campaign, described Mr Trump's remarks as a "major blow" for the prime minister.
"This is a Brexit bombshell and it has blown apart the whole government's post-Brexit trade strategy," she said.
"Even Donald Trump, not the sharpest tool in the box, knows this deal is a bad deal.
"Theresa May promised a Global Britain, but her Brexit is globally unpopular. Time to ditch this deal and let the people decide through a people's vote."
Others have also used Mr Trump's comments to criticise the prime minister's deal.
Brexiteer Tory MP Michael Fabricant tweeted: "Trump is spot on. It's a great deal for the EU."
Meanwhile, independent MP Charlie Elphicke simply called the president's comments "troubling".
With 90 or more Conservative MPs indicating they could vote against Mrs May's deal next month, Brexit Secretary Stephen Barclay admitted Mrs May faces a "challenging" division.