Objective:  Increased glucocorticoid metabolite excretion and enhanced expression and activity of 11β-hydroxysteroid dehydrogenase type 1 in adipose tissue are closely correlated to obesity and its detrimental consequences. Weight loss ameliorates the latter. The aim of this study was to explore whether increased glucocorticoid exposure in obesity is improved with substantial weight loss and thus is a consequence rather than a cause of obesity. Design and patients:  A prospective cohort study in 31 females. Measurements:  11β-HSD type 1- expression and -activity, urinary glucocorticoid metabolite excretion, body composition including regional adipose tissue depots and insulin resistance by HOMA-IR before and two years after gastric bypass surgery. Results:  After weight loss excretion of cortisol and cortisone metabolites decreased. Both cortisol and cortisone metabolite excretion correlated to central obesity, where the intraabdominal fat depot showed the strongest association. Cortisol metabolites correlated with 11β-HSD type 1-activity in abdominal subcutaneous adipose tissue. The ratio of cortisol to cortisone metabolites [(5α-tetrahydrocortisol (5αTHF) + tetrahydrocortisol (THF)+ α-cortol)/ (tetrahydrocortisone(THE)+ α-cortolone)] and the ratio of 5α-THF/ THF, both decreased after stable weight loss reflecting a down regulation of the net activities of 11β-HSD type 1 and 5α-reductase. Conclusion:  Long term weight loss in females is not only followed by reduced glucocorticoid production, but also favourably decreases the global and tissue specific activity of the cortisol-activating enzyme 11 β-HSD type 1, possibly contributing to the health benefits of bariatric surgery. © 2012 Blackwell Publishing Ltd.