Peaks of 31C (87.8F) across East Anglia and south-east England are expected on Friday and Saturday.
The Met Office said the main risk to health would come from stifling night-time temperatures of at least 20C (68F) in some places.
"It is the night-time values which are of real concern," said head of health forecasting Wayne Elliott.
"High humidity and the lack of any breeze could make matters worse for people with underlying health problems."
'Feel uncomfortable'
The Met Office's heat warning is set at level two out of four on its scale of how likely temperatures are to cause health problems.
Those at most risk from the hot weather are the elderly and babies and young children.
To keep cool, the NHS advises wearing loose cotton clothes, spraying or splashing faces and the backs of necks with cold water several times a day and staying in the coolest rooms of the house as much as possible.
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