Sir Ivan Rogers, Britain's ambassador, has unexpectedly resigned from his role, just months before negotiations with the EU were due to begin.
Rogers was due to finish his fixed-term role in October, but has told staff this afternoon that he will step down earlier than expected.
The news came as the government prepares to trigger Article 50 by the end of March. Having moved to Brussels in 2013, Rogers is one of the UK's most experienced EU negotiators.
However, in December he was roundly criticised after he warned in private briefings that the Brexit process could go on for 10 years.
A Foreign Office spokesperson said Rogers had departed early in order to allow a successor to be appointed before Article 50 is invoked.
"We are grateful for his work and commitment over the last three years," they added.
On Twitter, Sir Nicholas Macpherson, the Treasury's most senior civil servant between 2008 and 2016 described the exit as a "huge loss", accusing the government of "wilful and total destruction of EU expertise".
Macpherson also suggested that his successor at the exchequer, Tom Scholar, is "also out of the loop".
But Richard Tice, co-chair of Brexit campaign group Leave Means Leave, said: "Mr Rogers, like any similar civil servant, is paid to paint the extremes of possibilities. The key point, however, is that we are leaving two years after serving Article 50, with or without a trade deal.
"We can very happily revert to WTO rules which is what the vast majority of countries do with the EU."
Before he took on his role in Brussels, he was European and global affairs adviser, and has been credited with "being on first-name terms with most of the key backroom players in Berlin, Paris and other European capitals".
"Rogers' resignation makes a good deal on Brexit less likely," tweeted Charles Grant, the director of think tank the Centre for European Reform, today.