Background Liposuction can remove a substantial amount of body fat. We investigated the effects of liposuction of large volumes of fat on anthropometrics, body composition (BIA), metabolic hormones, and psychological measures in overweight/obese women. To our knowledge, this is the first study to examine both physiological and psychological changes following liposuction of large volumes of fat in humans. Method Nine premenopausal healthy overweight/obese women (age = 35.9 ± 7.1 SD, weight = 84.4 kg ± 13.6, BMI = 29.9 kg/m2 ± 2.9) underwent liposuction, removing 3.92 kg ± 1.04 SD of fat. Following an overnight fast, height, weight, waist, and hip circumferences were measured at baseline (one week pre-surgery) and post-surgery (wk 1,4,12). Blood samples were drawn for fasting concentrations of glucose, insulin, leptin, and ghrelin. The Body Shape Questionnaire (BSQ), Body Dysmorphic Disorder (BDD) Examination Self-Report (BDDE-SR), and Zung Self-Rating Depression Scale (ZDS) were administered. Results Body weight, BMI, waist circumference, and body fat consistently decreased over time (p < .05). Glucose did not change significantly, but insulin decreased from wk 1 to wk 12 (p < .05). Leptin decreased from baseline to wk 1 (p = .01); ghrelin increased but not significantly. Changes in body fat and waist circumference (baseline to wk 1) correlated positively with changes in insulin during that period, and correlated inversely with changes in ghrelin (p < .05). BSQ scores decreased significantly over time (p = .004), but scores for BDDE-SR (p = .10) and ZDS (p = .24) did not change significantly. Conclusion Liposuction led to significant decreases in body weight and fat, waist circumference, and leptin levels. Changes in body fat and waist circumference correlated with concurrent changes in the adipose-related hormones, insulin and ghrelin (baseline to wk 1), and body shape perception improved. Thus, besides the obvious cosmetic effects, liposuction led to several positive body composition, hormonal, and psychological changes.