Although plasma and 24 h urinary free cortisol (UFC) levels are normal in obese subjects, pharmacological investigations have identified minor hypothalamo-pituitary-adrenal axis differences in patients with abdominal body fat distribution (A-BFD) vs peripheral BFD (P-BFD). Using recent tools such as saliva cortisol or overnight urinary free cortisol upon creatinine ratio (UFC/UC) determinations, we have investigated a population of obese females according to their body fat distribution. In-patients subjects (no.=82) were subjected to routine biochemical testing, 24 h and overnight UFC/UC, basal and post-1 mg overnight dexamethasone-suppressing test plasma and saliva cortisol determinations. Central obesity defined by a waist-to-hip ratio (WHR) >0.85 was found in 64% of the subjects vs 87% when defined by waist girth (WG) corrected for age. Despite identical body mass index, A-BFD subjects were more prone to hypertension using both classifications and had higher triglycerides (WHR classification) or higher triglycerides, cholesterol and glycemia (WG classification). Plasma cortisol levels were similar but saliva cortisol levels were lower in the A-BFD group using the WG classification. The 24 h UFC/UC were similar but the overnight UFC/UC were higher in the A-BFD group using the WHR classification. These mild differences in cortisol nocturnal secretion and free cortisol indexes in subjects with different body fat mass distribution suggest that their hypothalamo-pituitary-adrenal axis has a spontaneously subtly different regulation.