Hospitals across Kent, Sussex and Surrey are being asked to discharge hundreds of patients who are well enough to leave by Friday.
The head of NHS South East, Anne Eden, said the beds are needed to deal with an expected surge in admissions of people ill with the Omicron variant.
The NHS nationally has agreed to a reduction of 30% of such patients based on the baseline figure of 13 December.
South East hospitals are being asked to make a 50% reduction by 31 January.
In a letter seen by the BBC, Ms Eden said: "This is in order to create the headroom to manage any further Covid pressures, with current modelling indicating a peak in Covid activity in mid-January."
She wrote: "It is now critical that we redouble our efforts to discharge those patients who no longer require bedded care, to create capacity, improve flow and reduce the pressure on staff."
Ms Eden said staff absences and the need to maintain delivery of critical care for patients mean the NHS "must continue to focus on creating the necessary capacity to meet demand".
"Failure to do this will significantly increase the risk of a further rise in patient harm," she said.
She said hospitals must work with partners, including social care providers, to achieve the reduction in the number of patients in hospital who were well enough to be discharged.
Source: BBC News, 10 January 2022