ObjectivePatients infected with the human immunodeficiency virus (HIV) have an increased risk of metabolic complications such as dyslipidaemia, insulin resistance and hypertension; symptoms that are also associated with an excess of the hormone cortisol. We studied the relationship between long-term cortisol levels and metabolic syndrome (MetS) in HIV-infected patients. DesignCross-sectional study performed at the outpatient clinic of infectious diseases of the Erasmus MC, University Medical Center Rotterdam, the Netherlands. MethodsFasting blood samples and anthropometric data were collected in 126 HIV-infected patients. An ELISA-based technique was used to determine long-term cortisol levels in scalp hair. Cortisol levels were compared to 191 healthy controls. ResultsA higher risk of MetS was observed in HIV patients with a low hair cortisol (odds ratio lower vs upper tertile 423, P=004). Hair cortisol levels were not significantly different between HIV patients and healthy controls (164pg/mg vs 135pg/mg; P=014). ConclusionThe risk of MetS was significantly higher in HIV-infected patients in the lowest hair cortisol group compared with patients in the highest hair cortisol group. This finding contrasts with results from studies in uninfected individuals where a high cortisol level in hair is associated with metabolic syndrome. The results of this study suggest that these metabolic complications might be related to relative cortisol hypersensitivity in HIV patients.