Four hundred jobs are being cut at the University of Manchester because it is £30m in debt.
Bosses say there will be no compulsory job losses. They are seeking volunteers for redundancy or early retirement.
In 2004, the university merged with the neighbouring Institute of Science and Technology to create one of Europe's biggest universities.
University president Alan Gilbert said some cutbacks were needed to ensure future growth.
The university now has 40,000 students and says it aims to become one of the best in the world by 2015.
Mr Gilbert said that one of its main problems is the number of staff taken on since the merger, swelling the workforce by a total of 2,800 people.
This has meant the annual budget has been hit by higher-than-expected wage increases, he added.
A large rise in utility costs have also combined to push the university £30m into the red.
But Mr Gilbert explained it has been preparing for the situation.
'Unavoidable challenge'
"Mergers always create unnecessary duplication," he said.
"In order to give the new institution two years to settle down a formal understanding was reached with the trade unions that the new university would delay any loss of jobs arising from any merger for two years.
"Ambitious agendas are never without cost. We now face the major, unavoidable challenge of addressing these two deficits in order to bring the university budget back into surplus."
Officials of the University and College Union, which represents lecturers, said they were in talks with the university.
Details about the voluntary redundancy and early retirement packages will be available later this month.