In the present study, we investigated the effects of a 6-month treatment with orlistat on body weight and lipid profile in 27 overweight women (mean body mass index [BMI]: 27.5 kg/m2; median age: 38.4 years) with mild hypercholesterolemia (total cholesterol: 225 mg/dl; low-density lipoprotein cholesterol [LDL-C]: 162 mg/dl). Orlistat was administered three times per day in conjunction with a hypocaloric diet After 6 months of treatment, body weight decreased by 17.71% and BMI decreased by 18.54%, whereas there was a significant (p < 0.01) improvement in serum lipid levels (total cholesterol: -25.33% LDL-C: -30.86%, high-density lipoprotein cholesterol: +9.37%, triglycerides: -35.97%). In conclusion, orlistat in combination with a low-energy diet seems to have a beneficial effect on body weight and lipid profile in overweight women with mild hypercholesterolemia.