Dr Elaine Munro will leave her position at the centre in February.
Gore Health chief executive Karl Metzler said her resignation would have an impact.
"Even if she is replaced, it will continue to impact both the general practice side and the accident and emergency department, as they have been under resourced."
The hospital had begun to feel the effects in the emergency department.
"We have had to look at putting additional nursing staff on duty in the A&E and we are looking at trying to secure additional staffing resource in the general practice as well."
This coincided with the growing demand in patients.
With the Mataura centre under pressure and short- staffed, an increase of acute primary care presentations to the emergency department had occurred for many months, he said.
Dr Munro’s resignation was announced in a letter sent to patients and the media.
It was sent by Te Hau o Te Ora, which is a partnership between WellSouth Primary Health Network, Hokonui Rūnanga and Awarua Whānau Services.
Mr Metzler agreed with the statement.
"There is a global shortage of GPs, compounded by our ageing Southland GP workforce, will make attracting GPs south incredibly challenging, even if we were offering world-class facilities and packages."
The Mataura centre role had been advertised locally, nationally and internationally.
From December 27, patients of the centre would be triaged over the phone and referred to a nurse, online doctor or a locum.
Mataura Community Board chairwoman Nicky Coats was contacted but said she was unable to comment as the matter was yet to be discussed by the board.
