Background Despite growing concerns about mental health during the COVID-19 pandemic, particularly in people with pre-existing mental health disorders, research has shown that symptoms of depression and anxiety were generally quite stable, with modest changes in certain subgroups. However, individual differences in cumulative exposure to COVID-19 stressors have not been yet considered. Aims We aimed to quantify and investigate the impact of individual-level cumulative exposure to COVID-19-pandemic-related adversity on changes in depressive and anxiety symptoms and loneliness. In addition, we examined whether the impact differed among individuals with various levels of pre-pandemic chronicity of mental health disorders. Method Between April 2020 and July 2021, 15 successive online questionnaires were distributed among three psychiatric case–control cohorts that started in the 2000s (N = 1377). Outcomes included depressive and anxiety symptoms and loneliness. We developed a COVID-19 Adversity Index (CAI) summarising up to 15 repeated measures of COVID-19-pandemic-related exposures (e.g. exposure to COVID-19 infection, negative economic impact and quarantine). We used linear mixed linear models to estimate the effects of COVID-19-related adversity on mental health and its interaction with pre-pandemic chronicity of mental health disorders and CAI. Results Higher CAI scores were positively associated with higher increases in depressive symptoms, anxiety symptoms and loneliness. Associations were not statistically significantly different between groups with and without (chronic) pre-pandemic mental health disorders. Conclusions Individual differences in cumulative exposure to COVID-19-pandemic-related adversity are important predictors of mental health, but we found no evidence for higher vulnerability among people with (chronic) pre-pandemic mental health disorders.