Case, who has served four prime ministers and 120 cabinet ministers in the role, said he would stay in post while the process to replace him got under way.
His long-planned departure on health grounds comes after a turbulent few weeks for the Downing Street operation marked by damaging leaks and internal rows, with Keir Starmer understood to have grown increasingly frustrated.
Cabinet ministers and senior aides have urged the prime minister to "get a grip" on the situation to avoid it undermining the government.
The departure of the UK's most senior civil servant, who is said to have had a tense relationship with Starmer's chief of staff, Sue Gray, gives the prime minister the opportunity for a reset.
Starmer thanked Case for his "support" and "years of service to our country" after the announcement, saying: "We are losing a public servant of the highest calibre.
"It is right that Simon takes time now to focus on his health, and he should know that he does so with the well wishes of this government and all those who he
The energy price cap, set by the industry regulator, Ofgem, and covering October to December, will rise by 10% to £1,717 a year for an average dual-fuel household in Great Britain paying by direct debit.
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