Introduction: Several theories have emerged in recent years suggesting that neuroendocrinological alterations, mainly changes in cortisol, could be of importance with respect to the link between chronic stress and disease. This study investigated possible deviations in the diurnal cortisol profiles of patients with clinically diagnosed stress-related exhaustion (exhaustion disorder – ED) compared with healthy controls. Material and methods: Salivary cortisol samples taken at home in the morning directly after waking up, 30 min later, and in the evening were compared between ED patients (N = 122; 25% men) and healthy controls (N = 98; 44% men). Follow-up measurements were performed after 6 months (79 patients) and 12 months (68 patients) of the treatment. Results: There were no clear differences in diurnal salivary cortisol profiles between the patients and healthy controls. Moreover, salivary cortisol levels and diurnal profiles did not change significantly during the treatment in the patient group. There was some indication of a smaller cortisol awakening response in the male patients compared to the male controls, but the difference appeared to be mainly related to the antidepressant use. Conclusions: Diurnal salivary cortisol profiles, at least as measured in this study, give a rather poor reflection of the prolonged stress exposure experienced by patients with ED. Such basal salivary cortisol measurements do not seem suitable as biomarkers for stress-related conditions such as ED or burnout, or as an aid to assess the effects of prolonged stress load in a routine clinical practice.