St John Ambulance will be making 250 employees due to a shortfall in funding caused by the coronavirus pandemic.
The charity are in the process of planning the redundancies, as they look to secure its long-term future.
The organisation is anticipating a £25m loss in 2020 and a further £20m in 2021.
Martin Houghton-Brown, chief executive, St John Ambulance says: “St John Ambulance is playing an important role in supporting hospitals and ambulance services with the national fight against Covid-19.
"However, we are a charity and have seen major sources of income dry up over recent months.
"This means that we need to reduce costs substantially, which might see around 250 people being made redundant in order to secure our survival and continue serving communities in future.
"We have benefited from government support as well as the furlough scheme but it is clear that we need to act sooner rather than later to protect our charity."