According to UCAS (admissions service) the number of people applying to study at UK universities has fallen by more than 4%, or 25,000, compared to last year.
There has been a slump in those applying to study nursing, while the number of mature students continues to fall in England and Northern Ireland. EU students planning to study in the UK is also down by 5%.
Fees in England will increase to £9,250 this year, and student loans are subject to an increase in interest rates - rising from 4.6% to 6.1% from this autumn.
University leaders said a number of factors could be behind the fall in applications including higher fees, funding changes from the NHS, and Britain's impending exit from EU membership.
From 1 August 2017, new nursing, midwifery and most other allied health students will no longer receive government bursaries - instead, they have to use the same student loans system as other students.
Sarah Stevens, head of policy at the Russell Group, said it would be a concern if students were being put off by Brexit:
"It's positive that applications from overseas students outside the EU have risen slightly.
International students bring social and cultural diversity to our campuses and this benefits all students, and they contribute £25.8bn to the UK economy."
The Department for Education said university applications from 18-year-olds was at record levels despite the overall fall reported by the number of applicants.