The University of Plymouth is cutting more than 200 jobs as part of its effort to reduce spending by £10m.
In all, 223 positions will go - 6.5% of the total workforce of 3,000.
The university said it was hoping to keep compulsory redundancies to a minimum and cut most jobs through "voluntary" means.
Unions said the announcement had caused distress and anxiety amongst staff and it would be wrong for the job cuts to be blamed on the economic downturn.
"Great distress and anxiety has been caused by this announcement"
University vice-chancellor and chief executive Professor Wendy Purcell said: "There will be the need for a small number of redundancies, however we hope to achieve the majority of these through voluntary means.
"We will do all that we can to minimise the number of compulsory redundancies."
Mike Sheaff, president of the university's branch of the University and College Union (UCU) which represents academic staff, said: "Great distress and anxiety has been caused by this announcement, particularly at a time when staff are working hard to welcome 30,000 new and returning students at the start of the academic year."
The union said it was "disingenuous" of the university to blame the job cuts on current economic difficulties as its budget deficit had been "allowed to build up" over recent years.
'Minimise impact'
A spokeswoman for Unison said members' jobs were its main concern, particularly in the current economic climate.
"We will ensure that we are fully consulted at all stages and work closely with the employer throughout the entire process to minimise the impact on our members and try to ensure that compulsory redundancies are avoided," she said.
Britain's General Union (GMB) also represents staff at the institution.
The University of Plymouth has about 30,000 students, which its management has said makes it one of the largest in England.
It is also a centre for research.
The job cuts will not affect staff at the Peninsula College of Medicine and Dentistry.
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