The number of people applying for a place at a UK university has fallen by around 25,000, according to admissions service Ucas.
The figures show a 4% decrease in UK applicants, while the number of EU students planning to study at a UK university or college has fallen by 5%.
One university leader said a number of factors could be fuelling the drop in numbers, including Brexit and funding changes for trainee nurses and midwives.
There has been a 2% rise in international students from countries outside the EU.
Across the UK, the numbers applying to go into higher education have fallen by 5% in England, 4% in Northern Ireland, 1% in Scotland and 5% in Wales.
However applicants from other overseas countries are up 2% and 18-year-olds in England applying to universities has reached a new high, with 37.9% planning to study for a degree, up from 37.2% in 2016.
The figures come amid a growing debate on the future of tuition fees, which currently stand at a maximum of £9,250 a year.
There have also been concerns that EU student numbers would be affected by the UK's decision to leave the Union.
Ministers have announced that EU students applying to start courses this autumn and next year will still be eligible for loans and grants, even if their course is due to finish after the UK's EU exit - which is due to be complete by March 2019.
Under recent changes, nursing students in England are now charged tuition fees, with NHS bursaries replaced with loans, which could also be a factor.
Dame Julia Goodfellow, president of vice-chancellors' group Universities UK, said: "Last year was a record high for applications,and factors such as Brexit and changes to the way degrees in nursing, midwifery and some other allied health professions in England are funded, could also be having an impact.
"There has also been a fall in the number of 18 and 19-year-olds across the UK population since 2010.
"This group makes up over half of all UK applicants to universities. The rate of applications from this age group, however, is at record levels, highlighting continued demand for university courses."
Dr Mark Corver, Ucas director of analysis and research, said: "The decrease in applicants is driven by falls from England, Wales and the EU, but applicants from other overseas countries are up 2%.
"Within the UK, older applicants are down, but applicants from the key 18-year-old age group have increased again to 321,950, supported by a record application rate from young people in England of 37.9%," he said.