Orlistat is a lipase inhibitor that is applied for treating obesity. Lipases are required for digestion and absorption of dietary lipids and fat-soluble vitamins and carotenoids. The aim of this study was to compare the effects of orlistat therapy on plasma concentrations of oxygenated (β-cryptoxanthin, lutein/zeaxanthin) and hydrocarbon (α-, β-carotene, lycopene) carotenoids. Six patients with a body mass index (BMI)≥30 kg/m² received 360 mg/d orlistat over 4.5 mon. Plasma carotenoid concentrations were determined at baseline (T ₀) and after 3 (T ₃) and 4.5 mon (T _4.5) along with anthropometric, dietary, and biochemical indices, including plasma lipids, retinol, α- and γ-tocopherols, and FA. Baseline BMI was 32.7±1.97 kg/m². Five of six patients lost weight; the average weight loss was 3.6±2.4% (P=0.47). There were no significant changes in dietary carotenoid intakes. In contrast, plasma α-and β-carotene concentrations decreased significantly from T ₀ to T _4.5 by 45% (P=0.006) and 32% (P=0.013), respectively. Plasma lycopene decreased from T ₀ to T ₃ but increased again from T ₃ to T _4.5, while β-cryptoxanthin and lutein/zeaxanthin concentrations did not change. There were no significant alterations in tocopherol, retinol, and FA concentrations. In conclusion, even though weight loss was not significant, orlistat therapy was associated with significant decreases in plasma concentrations of the highly lipophilic hydrocarbon carotenoids, α- and β-carotene.