Background: Acne vulgaris is a common chronic skin disease involving blockage and/or inflammation of pilosebaceous units (hair follicles and their accompanying sebaceous gland). Desnutrin is the major triglyceride lipase in the adipose tissue of mice and excessive secretion from adipocytes results in decreased triacylglycerol storage and increased lipolysis, fatty acid oxidation and thermogenesis. Objective: The aim of this study is to evaluate serum level of Desnutrin in acne vulgaris patients and correlate it with disease severity. Patients and Methods: This study was performed on 40 patients with active acne lesions and 40 healthy subjects with no previous history of acne and no active acne lesions as controls. The control group was composed of age, gender, and Body mass index (BMI) matched individuals. All the patients were recruited from the outpatient clinic of Dermatology & Venereology Department, Ain Shams University hospitals, from March 2016 till August 2016.Serum desnutrin assessment was done by ELISA kit using Sandwich-ELISA as a method. The Micro elisa stripplate has been pre-coated with a Horse Radish Peroxidase antibody specific to desnutrin. The optical density was measured spectrophotometrically. Results: There was a significantly lower level of serum desnutrin among cases compared to that of control group, while the fasting blood glucose level was significantly higher among cases compared to that of control group. The collective data from both study groups showed a significant negative correlation between the mean serum fasting blood glucose level and desnutrin level. There was no significant correlation between the severity of acne and serum desnutrin level. Conclusion: The level of serum desnutrin can affect the occurrence and the progression but not the severity of acne among susceptible individuals. The level of fasting blood glucose is also of value regarding the occurrence of acne and has a negative effect on the level of desnutrin.