BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in the pathophysiology of post-traumatic stress disorder (PTSD). However, there has been little study of HPA stress reactivity in association with PTSD symptoms (PTSS) in children; and there is limited research on PTSD in low and middle-income countries, where trauma exposure is more common and co-occurring stressors more likely. METHOD: We assessed the relationship between PTSS and cortisol stress reactivity in children aged 13 years (N = 291) from an impoverished South African community. HPA axis stress reactivity was indexed by salivary cortisol during the Trier Social Stress Test (TSST). RESULTS: In regression analyses both trauma exposure and PTSS showed small inverse associations with total cortisol output (area under the curve with respect to ground) during the TSST, but PTSS effects did not withstand correction for covariates. In addition, hierarchical linear modelling (HLM) found that PTSS were associated with alterations in the shape of the profile of cortisol reactivity that were moderated by sex. In girls, PTSS were associated with reduced linear slope but larger quadratic slopes, whereas the opposite pattern was found in boys. Thus, elevated PTSS were associated with overall blunted profiles of cortisol stress reactivity in girls, but a larger quadratic slope in boys reflects a steeper cortisol increase and decline in boys. There was no relationship between trauma exposure (with or without PTSS) and cortisol reactivity profiles in HLM analyses. CONCLUSION: In children from a high adversity, low and middle income country context, sex specific associations were found between PTSS and cortisol responses to psychosocial stress. Further research should probe HPA axis functioning more comprehensively in such populations to understand the biological associations of PTSS