BackgroundAllostatic load (AL) is an objective measure of the biological components of chronic stress within clinical practice, potentially influencing depression, anxiety, and suicide. This study investigates the association between AL and these mental disorders. MethodsIn this cohort study of 333,017 adults, participants without prior diagnoses of depression, anxiety, or suicide were observed from March 13, 2006, to October 31, 2022. AL was estimated using 10 biomarkers reflecting metabolic, cardiovascular, and inflammatory dysregulation. Diagnoses were based on the International Classification of Diseases 10th Revision (ICD-10). We performed Cox proportional hazards models to assess the relationship between AL and these mental disorders. Additionally, we conducted subgroup analyses for sex, age, and Townsend Deprivation Index (TDI), along with sensitivity analyses. ResultsThe median follow-up period was 12.99 years. Over the follow-up period, 13,441 (4.04%) participants developed depression, 13,903 (4.17%) developed anxiety and 796 (0.24%) committed suicide. In fully adjusted model, individuals with high AL had an increased risk of depression (HR = 1.389, P = 8.38 ×10-27), anxiety (HR = 1.304, P = 5.82 ×10-19) and suicide (HR = 1.433, P = 4.46 ×10-3). Women and younger individuals with high AL were vulnerable to depression and anxiety, while moderate AL levels were significantly associated with suicide in men and younger participants. Moreover, individuals with middle and high AL had an elevated risk of comorbid depression and anxiety. ConclusionsHigh AL is positively associated with increased risks of depression, anxiety, and suicide, highlighting its potential as a predictive tool in mental health.