At MSD, workers affected will be in the Service Delivery and Māori Communities and Partnerships teams, as well as those in HR, policy, strategy and communications.
The Public Service Association said the voluntary redundancies along with vacant roles not being filled could see hundreds of workers leave.
The PSA represents about 400 ministry staff and national secretary Kerry Davies said such a big cull was heartless and cruel.
It could also destabilise the health system, she said.
“A lot of these people have been working for the ministry and formed very strong bonds - particularly during the Covid period, giving their all to meet the demands of that pandemic crisis for New Zealand.
“The work that is needed to prepare for the health needs of the country - that’s really serious, important work. It’s the backbone of the health system.”