Matt Hancock is due to face MPs a day after his handling of the pandemic was fiercely attacked by the prime minister's former senior aide.
Dominic Cummings described the health secretary as "completely incapable of doing the job" and said he "should have been fired" for lying.
He criticised Mr Hancock over PPE shortages and "stupid" testing targets.
A spokesman for Mr Hancock said: "We absolutely reject Mr Cummings' claims about the health secretary."
Communities Secretary Robert Jenrick told BBC Breakfast Mr Hancock and others had been "working round the clock to try to do the best they could for the country".
Mr Jenrick also said it was "sensible" for the independent inquiry into the government's handling of the pandemic to begin in spring 2022, when the UK was out of the "response phase".
But Labour's deputy leader Angela Rayner said the inquiry should begin immediately, saying Mr Cummings' claims were "incredibly devastating to hear".
She added that Mr Hancock was facing serious allegations and must "justify how we ended up in these circumstances".
The health secretary's spokesman said Mr Hancock had not seen the evidence session in full and would continue working closely with the prime minister.
Mr Hancock will appear in the House of Commons at around 10:30 BST to answer an urgent question tabled by Labour about the government's handling of Covid.
He is also expected to lead a coronavirus press conference later in the day.
Labour's shadow health secretary Jonathan Ashworth said Mr Cummings' "very grave allegations" appeared to be "well-founded" and the health secretary would have to "give us an explanation" in order for the country to "maintain confidence in him".
Mr Cummings left his role in Downing Street towards the end of 2020 following a power struggle inside No 10 and has since been highly critical of the government.
The former Brexit campaigner used his lengthy evidence session to the health and science select committees on Wednesday to portray a government unprepared for the pandemic and slow to act when it hit.
He argued that mistakes meant "tens of thousands of people died, who didn't need to die".
Professor Neil Ferguson, whose modelling was crucial to the government's decision to go into the first lockdown, was asked whether he agreed with the claim.
Prof Ferguson reiterated his previous comment that locking down a week earlier in March 2020 would have saved around 20,000-30,000 lives. "I think that's unarguable. The epidemic was doubling every three to four days in the weeks 13-23 March," he told the Today programme.
During the seven-hour appearance, Mr Cummings was particularly scathing about Mr Hancock, arguing that he "should have been fired for at least 15 to 20 things including lying to everybody on multiple occasions in meeting after meeting in the Cabinet Room and publicly".
On care homes, he said: "Hancock told us in the Cabinet Room that people were going to be tested before they went back to care homes... we only subsequently found out that that hadn't happened.
"Now the government rhetoric was 'we put a shield around care homes' and blah blah blah - it was complete nonsense."
Mr Cummings also attacked Mr Hancock for setting a "stupid" target of offering 100,000 Covid tests a day, saying it "hugely disrupted" efforts to "properly" establish a testing system.
"Hancock wanted to be able to go on TV and say 'look at me and my 100k target' - it was criminal disgraceful behaviour that caused serious harm," he said.
On PPE provision, Mr Cummings described the situation as a "disaster" with "hospitals all over the country" running out of supplies, despite assurances from the health secretary that "everything is fine".
He added that the head of the civil service said: "I have lost confidence in the secretary of state's honesty in these meetings."
Not the prime minister, nor the health secretary, nor the government's top scientists, nor the Whitehall machine, nor even Mr Cummings himself, escaped the barbs today.
The hours of testimony gave a disturbing sense of an administration simply overwhelmed by the scale of the Covid crisis at the start of last year - scrambling, and failing to keep up on many fronts.
It is the first time that one of those involved in making the decisions during those risky months has admitted in public that so many mistakes were made.
It is the first time that some of Boris Johnson's most controversial alleged comments about Covid have been put on the record, despite the prime minister's denial.
And it is the first time, most importantly perhaps, that someone who wielded significant power has said publicly that tens of thousands of people lost their lives in this country unnecessarily.
Imagine what that must have felt like for a bereaved family, or care home staff to hear.
Committee chairman Greg Clark told Mr Cummings he should provide written evidence to back up his claims about Mr Hancock, who will be questioned by the committee in two weeks' time.
Speaking at a Politico Live event, International Trade Secretary Liz Truss defended Mr Hancock as "an excellent colleague who is doing a very good job in what has been a very tough global pandemic".
Mr Cummings also attacked Boris Johnson, describing his former boss as "unfit for the job" and claiming he had ignored scientific advice and wrongly delayed lockdowns.
Asked if the prime minister had said he would rather see "bodies pile high" than take the country into a third lockdown, as reported by the BBC, Mr Cummings said: "I heard that in the prime minister's study."
Mr Johnson has denied making the comments and on Thursday morning Number 10 said the prime minister would be "getting on with the job" by visiting a hospital.
Speaking during Prime Minister's Questions, Mr Johnson insisted the government's priority had always been to "save lives".
He added that "none of the decisions had been easy" but that his government had followed "the best scientific advice that we can".
Mr Cummings began his evidence by apologising to "the families of those who died unnecessarily", adding: "Senior ministers, senior officials, senior advisors like me fell disastrously short of the standards that the public has the right to expect".
He said those on the front line of the pandemic were like "lions" being "led by donkeys".
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Mr Cummings also told the committee:
- A herd immunity strategy was dropped when the likely death toll became clear
- His trip to County Durham during the lockdown "undermined public confidence"
- The PM had offered to be injected "live on TV with the virus" to show the public there was nothing to fear
- The running of the government "kind of collapsed" when Mr Johnson was hospitalised with Covid
- The PM's fiancee Carrie Symonds "wanted to get rid of" him
More than 127,000 people have died in the UK with 28 days of a positive test since the start of the pandemic, according to the government's coronavirus dashboard.
In a separate development, a Downing Street source suggested that a Covid recovery summit with the first ministers of the devolved nations had been postponed because other leaders needed more time to prepare.
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2021-05-27 06:07:12Z
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