Matt Hancock and Gavin Williamson's jobs are said to be under threat as Boris Johnson plans a reshuffle to attempt to draw a line under the power struggle in Downing Street.
Senior sources in No 10 suggested the Prime Minister is now preparing for big changes to his teams both in No 10 and the Cabinet, with a ministerial reshuffle expected by January.
Health Secretary Mr Hancock and Education Secretary Mr Williamson were both thought to be vulnerable after they saw major policy disasters including contact-tracing and the A-level results fiasco.
Mr Johnson will try to reassert control over his Government by meeting with concerned Tory MPs after two of his closest aides left Downing Street.
Chief adviser Dominic Cummings exited Number 10 amid claims he had briefed against Mr Johnson and the PM's fiancee Carrie Symonds.
His departure followed the resignation of Lee Cain as communications chief earlier this week.
Sources said the PM will now "attempt to get his premiership back on track" by establishing a policy board that will appeal to Northern working class voters who helped him win last year's general election.
The group will be chaired by Tory MP Neil O'Brien, who helped former chancellor George Osborne devise the Northern Powerhouse.
Leading Tory MPs have urged the PM to use the change of personnel to "reset the Government" following complaints the party and Parliament were not being heard during the time Mr Cummings held sway.
Former PM Gordon Brown has said infighting in Downing Street must end as the UK deals with the coronavirus pandemic.
"You've got 27,000 new cases yesterday, 500 deaths, you've got a million young people looking for work, you've got people without savings planning for Christmas. Really we should not be seeing this factional fighting at the moment," he said.
