The Irish Nurses and Midwives Organisation and the Psychiatric Nurses Association have served notice of industrial action in the Donegal Intellectual Disability Services, Ard na Gréine in Stranorlar.
The action, in the form of a work-to-rule, is due to begin on 2 June.
INMO and PNA members will also stage a lunchtime protest on 27 May.
Both unions balloted members after the HSE withdrew a proposal to provide 24/7 on-site management.
In a statement, the INMO said that for two years, local HSE management promised that robust out-of-hours governance would be reinstated.
It said, based on a written commitment, nursing staff cooperated with a major reconfiguration of services, including the transfer of vulnerable residents to two new residential houses.
The INMO and PNA are seeking the restoration of on-site management, which they said was removed without consultation after 2016.
They are also calling for additional nursing managers to provide clinical authority for service-wide safeguarding.
INMO Assistant Director of Industrial Relations, Colm Porter, said the decision to take industrial action in Ard na Gréine had not been taken lightly.
"It is clear that ensuring appropriate governance structures are in place in intellectual disability services must be an immediate priority for the HSE," he said.
PNA Industrial Relations Officer, Niall O'Sullivan, said it is unacceptable that "members in Ard na Gréine are operating in a leadership vacuum".
"Report after report into intellectual disability services have proved that governance structures cannot be disregarded," he said.
In a statement, the HSE said it has been notified by the PNA and INMO of their intention to begin industrial action at Ard na Gréine Court Intellectual Disability Services.
It said it held talks with both unions over recent months to reach an agreement on the issues, with a further meeting due to take place this week.
The HSE said it remains committed to engagement with staff and the unions to reach a resolution to the issues.
