Post-traumatic stress disorder (PTSD) has been associated with dysregulation of the neuroendocrine system. In this study we examine the effects of psychotherapy in 21 PTSD patients, with and without coexisting depression, on the levels of six stress-related hormones: cortisol, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-sulfate (DHEA-S), prolactin, thyrotropin (TSH) and free thyroxin (fT4). The results show that after brief eclectic psychotherapy (BEP) significant changes occurred in levels of cortisol and DHEA. Responders showed an increase in cortisol and DHEA levels, while in non-responders both hormone levels decreased. Differences were only found after controlling for depressive symptoms. In conclusion, effective psychotherapy for PTSD may alter dysregulations in the Hypothalamus–pituitary–adrenal (HPA)-axis, but comorbid depressive symptoms should be taken into account.