NHS Barnsley has announced it is to make nearly £6m of savings over the next three years, resulting in the loss of at least 35 jobs.
The primary care trust said it was required to make a 43% saving on management costs, equating to total savings of £5.9m.
The trust said it was "unfortunate but inevitable" that there would be an impact on jobs.
Unions said they would work with the trust to represent members' concerns.
The trust said the cost savings had been identified following a review of management costs, as required by the government.
The 35 redundancies are part of £1.6m of savings identified for the current financial year.
NHS Barnsley said it was unable to determine at this stage whether further jobs cuts would be made, but it hoped the present job losses would be made through voluntary redundancies.
In a statement the trust said: "It is unfortunate but inevitable that when making cost savings on this scale there is likely to be an impact on jobs."
Chief executive of NHS Barnsley, Ailsa Claire, said: "These are very difficult and uncertain times for everyone and we understand that our staff and local people will be concerned about jobs and the health services we provide.
"Because of this we need to put measures in place quickly to minimise job losses and protect local health services for Barnsley residents. We are working hard to ensure we make cost savings with as little disruption as possible."
Paul Smith and Tony Wright, of the join trade unions body Staff Side, said: "We fundamentally disagree with the decision to impose this 43% cut when our organisation is already one of the most successful and efficient within the Yorkshire and Humber region.
"However, given that this cut is inevitable we support the decision of the board to seek to avoid compulsory redundancies."