Teenagers who struggle with depression significantly underachieve at GCSE, according to new long-term study.
The King's College, London, team suggested pupils affected be allowed to stagger or postpone their exams.
It comes at a time when rates of children's mental health are expected to increase due to experiences during the Covid lockdown.
Data on rates of children's mental health referrals during the lockdown period is not yet available.
But many voluntary agencies working with young people say they have seen requests for support increase.
And ministers are currently deciding how they can hold exams, including GCSEs, next year that are fair to those who have missed out on education during the lockdown and beyond.
The research, led by King's PhD student Alice Wickersham, tracked the educational results of about 1,500 children over seven years between 2007 and the end of 2013.
All had received a diagnosis of depression before the age of 18, with the most common age being 15.
The findings showed a worrying picture of children who did well at primary school, but whose attainment dipped in secondary as they progressed towards GCSEs.
Some 83% reached the expected level of attainment at age six or seven, and over three-quarters met it at the end of primary school.
But by the time these children reached Year 11, only 45% achieved the then benchmark of five good GCSEs including English and maths.
Ms Wickersham, from the National Institute for Health Research at the Maudsley Biomedical Research Centre, said previous studies had found depression in childhood is linked to lower school performance.
She said: "What we've observed is that a group of children and adolescents who developed depression at secondary school had performed quite well when they were in primary school.
"It is only when they sat their GCSEs that they tended to show a drop in their school performance, which also happened to be around the time that many of them were diagnosed."
She added that while this would not be the case for all teenagers with depression, it does mean many find themselves at a disadvantage for "this pivotal educational milestone".
"It highlights the need to pay close attention to teenagers who are showing early signs of depression," she said.
"For example, by offering them extra educational support in the lead up to their GCSEs, and working with them to develop a plan for completing their compulsory education."
The study suggests allowing such candidates to stagger their exams or even delay them, if necessary.
A Department for Education spokesman said: "Testing has always been an important part of education, but it should never be at the expense of a young person's wellbeing.
"The government has invested significantly in mental health charities and in support for teachers and young people, including a new £8 million training programme run by experts to tackle the impact of coronavirus on pupils, parents and staff.
"We trust schools to make sure that pupils get the help and support they need, when they need it, working with parents to do this."
But Julie McCulloch, director of policy at the Association of School and College Leaders, said funding pressures had reduced the amount of money available for pastoral and mental health support in schools.
She added: "There have also been significant problems in accessing local mental health services for young people who are in need of specialist treatment.
"It is very likely that the Covid crisis will have led to more young people experiencing mental health issues.
"Schools are doing their very best to support these pupils but the pressures on the system are hardly the best starting point.
"We recognise that the government is endeavouring to improve mental health support for young people, but we remain concerned that schools just do not have the funding they need for this and many other tasks."
Campaigns director at Young Minds Tom Madders said: "We know many children and young people have struggled with their mental health as a result of the pandemic, and ensuring that effective support is available in the coming months is crucial.
"If the government wants children to catch up academically after months away from school, it should provide ring-fenced funding for schools to support student mental health."