<b><i>Introduction:</i></b> Cortisol is involved in the regulation of gluconeogenesis and glucose utilization. In morbid obesity (MO), the association of cortisol excretion with metabolic parameters is not well-characterized. In our study, we evaluated cortisol excretion in nondiabetic subjects with MO and its effect on glucose metabolism. <b><i>Methods:</i></b> We included 1,249 nondiabetic patients with MO (79.8% females, mean BMI 44.9 ± 6.5 kg/m<sup>2</sup>, mean age 38 ± 11 years). Anthropometric data and cardiovascular risk factors were assessed, and an oral glucose tolerance test for calculation of insulin resistance was performed. Cortisol excretion was assessed on 2 consecutive days (24 h urine specimens). <b><i>Results:</i></b> Regarding cortisol excretion, patients were divided into 3 tertiles (urinary cortisol ≤51.6, >51.6 and <117.6, and ≥117.6 μg/24 h, respectively). Patients in the highest tertile were younger (<i>p</i> = 0.003), more obese (BMI: <i>p</i> = 0.040), had lower diastolic blood pressure ([DBP]; <i>p</i> = 0.012), lower total (<i>p</i> = 0.032) and LDL cholesterol (<i>p</i> = 0.021), fasting (<i>p</i> = 0.049) and 2-h glycemia (<i>p</i> = 0.028), 2-h insulinemia (<i>p</i> = 0.020), and HbA1c (<i>p</i> < 0.001), and a higher estimated glomerular filtration rate (eGFR) (<i>p</i> < 0.001). The glucose (<i>p</i> < 0.001) and insulin (<i>p</i> = 0.011) area under the curve (AUC) were also lower. Urinary cortisol excretion adjusted for age, sex, and eGFR was positively correlated with body weight (BW, beta = 0.076, <i>p</i> = 0.004) and overall glucose tolerance (oral disposition index, beta = 0.090, <i>p</i> = 0.011), and negatively with HbA1c (beta = −0.179, <i>p</i> < 0.001), 2-h glycemia (beta = −0.075, <i>p</i> = 0.032), AUC glucose (beta = −0.103, <i>p</i> = 0.002), and DBP (beta = −0.139, <i>p</i> < 0.001). HbA1c, BW, and DBP remained significant after multivariable analysis. <b><i>Discussion/Conclusion:</i></b> Despite being more obese, patients with higher cortisol excretion have a more favorable metabolic profile. These results deserve further attention regarding the respective mechanisms.
