Background: Exposure to early adversity has been associated with long-lasting risks for poor health and functioning. Prior research suggests that the hypothalamic-pituitary-adrenal (HPA) axis, and its main end-product glucocorticoid hormone cortisol, may be at play. This study tested whether an index of cumulative socioeconomic and psychosocial adversity assessed prospectively, from infancy to adolescence, was associated with hair cortisol concentration (HCC), and if this association differed by sex. Methods: The sample comprised 556 adolescents (42.0% males) who provided hair for cortisol measurement at 17 years of age. Adversity indicators (young and single motherhood, low socioeconomic status (SES), maternal alcohol use, hostile-reactive parenting, and depressive symptoms, as well as peer victimization and neighborhood dangerousness) were repeatedly reported by mothers or youths between the ages of 5 months and 15 years. Results: Chronic adversity was non-linearly associated with HCC; youth exposed to lower and higher levels of adversity had moderate-to-higher HCC compared to lower HCC noted in participants with moderate levels of adversity, for both males and females. None of the indicators taken separately, except the perception of neighborhood dangerousness, were significantly associated with HCC. Conclusion: Our findings support the hypothesis that HPA axis activity varies according to cumulative adversity, albeit non-linearly, which may bear consequences for later health and functioning.Read less <