Brexit: Where now for the 'special relationship'?
This is not the decision the Obama administration had hoped for. It also wasn't the result the president had helped campaign for.
He warned the UK in April that a vote to leave the EU would put them at the "back of the queue" when it came to trade deals with the US.
The country was stronger and safer as part of something bigger, he said.
Mr Obama has since softened his language - in a statement, he said the so-called "special relationship with Britain will endure".
But he also praised the European Union for fostering the "spread of democratic values and ideals" - a line that could be interpreted as a dig to remind the UK about the club from which it had just resigned.
"Brexit" has left the president pledging to be friends to two parties in the middle of what could be a messy divorce. He and German Chancellor Angela Merkel "regretted" the decision by the British people, the White House said.
And then there is the political fallout. Mr Obama and the woman who'd like to be his successor, Hillary Clinton, will be casting an eye across the Atlantic and wondering at the success of the "leave" campaign.
The Republican nominee Donald Trump said the vote proved that "people want to take their country back. They want to have independence in a sense".
When you listen to some of those who voted to leave the EU, he appears to be right.
These are the voices of hard-working men and women who are saying "no more" to big government or big business. They are wary of being dictated to by other countries.
British voices on Brexit
The same phrases are used in the US on the election campaign trail about Washington. Instead of Brussels, it's the US capital that is provoking this rage.
It is the same kind of disenfranchised electorate that has been inspired by the campaigns of anti-establishment politicians such as Donald Trump and Democratic Senator Bernie Sanders.
It's also an isolationist viewpoint that President Obama has fought so hard to diminish.
The message from the White House may be almost "keep calm and carry on".
But this vote is yet another indication that politics in the US and around the world is no longer business as usual.