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Objective: Hypercortisolism is a risk factor for obesity. Cortisol increases in response to food intake in lean subjects. In obese subjects, disturbances of the food-induced cortisol peak were reported, but data from sufficiently powered and well-controlled trials are lacking. Understanding the cortisol response to food is essential as amplified or recurrent cortisol surges could lead to hypercortisolism and contribute to obesity. Therefore, we investigate the cortisol response to food in lean and obese subjects. Design: This is a non-randomized, open-label study. Methods: We assessed serum cortisol values after a high-calorie meal in lean and obese male subjects. Cortisol levels were frequently assessed before and for 3 h after food intake. Results: A total of 36 subjects (18 lean and 18 obese) were included. There was no difference in overall cortisol levels between both groups during the study (area under the curve (AUC) obese: 55,409 ± 16,994, lean: 60,334 ± 18,001, P = 0.4). Total cortisol levels reached peak concentrations 20 min after food intake in both groups; the maximum cortisol increase was similar in both groups (cortisol increase obese: 69.6 ± 135.5 nmol/L, lean: 134.7 ± 99.7 nmol/L; P = 0.1). There was no correlation between body mass index and baseline cortisol values (R2 = 0.001, P = 0.83), cortisol increase (R2 = 0.05, P = 0.17), or cortisol AUC (R2 = 0.03, P = 0.28). Conclusions: This study demonstrates that high-calorie food intake causes an immediate and substantial cortisol response in lean and obese subjects and is independent of body weight. Significance statement: This study demonstrates that high-calorie food intake causes an immediate and substantial cortisol response in lean and obese subjects, independent of body weight. In contrast to the current literature, our findings show that the physiological cortisol response to food is intact in obesity. The substantial and prolonged increase further supports the hypothesis that frequent high-calorie meals cause hypercortisolism and aggravate weight gain.