Matt Hancock has cast serious doubt over the 21 June target date for ending the coronavirus lockdown.
The health secretary, speaking in the House of Commons on Thursday, told MPs "it’s too early now to say" whether the government will be able to lift all legal restrictions in England on this date.
It comes amid the spread of the more transmissible B.1.617.2 variant of the virus, first identified in India.
Hancock was appearing in the chamber after his handling of the pandemic was repeatedly attacked by Dominic Cummings, Boris Johnson's former chief adviser, at a committee hearing on Wednesday. He said the “unsubstantiated allegations” from Cummings “are not true”.
However, he was also asked about the Indian variant and said: "It is true the Indian variant is spreading across the country. Estimates vary as to what proportion of the new cases each day are the variant first identified in India, which is more transmissible.
"My assessment is, it’s too early now to say yet whether we can take the full step four on 21 June.
"I desperately want us to but we’ll only do that if it’s safe. We will make a formal assessment ahead of 14 June as to what step we can take on the 21st."
There had been 3,180 new Covid-19 cases as of 9am on Wednesday, up 687 from the day before.
Hancock's gloomy outlook came after Prof Neil Ferguson, the scientist whose modelling convinced the government to impose the first lockdown, also told BBC Radio 4’s Today programme that the 21 June date "is rather in the balance"
He said: “The key issue as to whether we can go forward is will the surge caused by the Indian variant – and we do think there will be a surge – be more than has been already planned in to the relaxation measures?
“So it was always expected that relaxation would lead to a surge in infections, and to some extent a small third wave of transmission... [but] we can’t cope with that being too large.
“In the next two or three weeks we will be able to come to a firm assessment of whether it’s possible to go forward.”
Prof John Edmunds, speaking on ITV's Peston show on Wednesday night, was also asked if Boris Johnson should unlock on 21 June.
"No," he said.
"At the moment, anyway, it looks a little bit risk of course. The Indian variant is taking off in a number of places."
He added people are still at less than half of their "normal contact patterns" which is currently "helping keep a lid" on the variant.
"Encouraging people to go back to normality would be very rash at the moment, so I hope that doesn't happen for a little while at least."
Watch: Five important moments from Dominic Cummings' testimony