The role of cortisol as a premorbid vulnerability factor for trauma sequelae remains unclear. Furthermore, the onset of long-term endocrine changes in response to first-time trauma as a function of later psychopathology is not clarified yet. Thus the predictive value of pre- and post-traumatic hair cortisol concentrations (HCCs) for psychological trauma sequelae was investigated in response to motor vehicle crash (MVC). A total of N= 62 MVC survivors participated in this study (46 females, mean age (SD): 43.94(12.95)). Subsequent trauma sequelae were measured with a structured clinical interview and self-report questionnaires to evaluate psychological symptoms (pre-MVC and three months post-MVC). Hair strands were taken immediately after MVC and three months post-MVC, reflecting cumulative cortisol secretion over the three-month period before and after the MVC. A total of 22.6% of the participants developed a trauma sequela with an affective disorder (14.5%) and/or anxiety disorder (16.1%). We observed a significant main effect of group and diagnosis × time interaction with an increase of HCC in those individuals who presented a subsequent psychiatric disorder. Regression analyses revealed that post-MVC increased HCC were significantly predictive of higher levels of subsequent depressiveness, and that pre-MVC increased HCC were predictive of higher levels of subsequent avoidance behavior. Our findings demonstrate that individual differences in long-term cortisol secretion in response to a first-time traumatic event (MVC) contribute to subsequent psychopathology. Specifically, higher long-term cortisol secretion before and after first-time MVC was a risk factor for subsequent development of avoidance behavior and depressiveness, respectively.Lay summaryHigher cortisol secretion and stress experience before a motor vehicle crash was a risk factor for subsequent development of psychological symptoms.