Professor Neil Ferguson has resigned from the government's scientific advisory group (SAGE) after he broke coronavirus lockdown rules.
In a statement announcing his departure, the leading epidemiologist from Imperial College London said he had made an "error of judgement".
It followed claims in The Telegraph that he allowed a friend reported to be his lover, Antonia Staats, to visit him at home - in breach of official rules he contributed to devising.
As a prominent member of SAGE, his resignation represents a blow for the group and ministers he is helping guide policy around the COVID-19 pandemic.
"I accept I made an error of judgement and took the wrong course of action," he said.
"I have therefore stepped back from my involvement in SAGE.
"I acted in the belief that I was immune, having tested positive for coronavirus and completely isolated myself for almost two weeks after developing symptoms.
"I deeply regret any undermining of the clear messages around the continued need for social distancing to control this devastating epidemic.
"The government guidance is unequivocal, and is there to protect all of us."
Security minister James Brokenshire said the senior scientist "made the right decision" and the government will "continue to be informed" by SAGE.
He dismissed Prof Ferguson's claim he thought he was immune, telling Sky News' Kay Burley@Breakfast: "It's far too early to make those judgements."
The news comes a month after Dr Catherine Calderwood quit as Scotland's chief medical officer after making two trips to her second home.
While SAGE has around 50 members, Prof Ferguson had become one of the most prominent after featuring in some of the government's regular coronavirus briefings.
He first made headlines in mid-March when an Imperial College study, of which he was lead author, warned 250,000 people could die if the UK did not enforce social-distancing measures.
Less than a fortnight ago, Prof Ferguson said life "cannot go completely back to normal" and that social distancing would need to remain until a vaccine was developed.
Then, he warned that more than 100,000 people could die this year if the lockdown was lifted so only elderly and vulnerable people were shielded.
Prof Ferguson said he was "very sceptical" that a scenario where the younger population resumed a normal life would be a "viable strategy".
On 18 March, he reported having the fever and cough symptoms of COVID-19 and that there was a small risk he had infected others.