Energy drinks were originally designed for active sportsmen. However, they are also widely used by inactive people. PURPOSE: To investigate the effect of 4 weeks energy drink consumption on whole body and peripheral insulin sensitivity, and metabolism in sedentary individuals. METHODS: Twelve healthy, physically inactive participants without history of regular soft drink consumption (5 males and 7 females, 26 ± 6 yrs and BMI = 21.7 ± 1.5) underwent a 4 week energy drink supplementation. The increase in carbohydrate intake by energy drink consumption was adjusted to 2.1 ± 0.2 g/kg body weight (approximately 760 ml per day). Participants were instructed to maintain and record their usual diet before, during and after the intervention. Pre- and post-test measures were indirect calorimetry, fasting blood glucose and insulin, body composition, and a muscle biopsy one hour after 75 g glucose ingestion for metabolic enzyme and signalling protein detection. Post-tests were carried out 32 hours after the last beverage was consumed. RESULTS: There was a trend for an increase in total body weight (65.5 ± 9.6 vs. 66.6 ± 10.5 kg, p = 0.079, hp2 = 0.254). Fat mass increased significantly (15.7 ± 5.1 vs. 16.8 ± 4.9 kg, p = 0.012), lean mass did not change (2.58 ± 0.57 vs. 2.58 ± 0.58 kg). Fasting respiratory exchange ratio (RER) increased significantly (0.75 ± 0.09 vs. 0.87 ± 0.08, p = 0.039) as did fasting plasma glucose (4.81 ± 0.40 vs. 5.10 ± 0.35 mmol/l, p = 0.012). There was a strong trend towards an increase in fasting plasma insulin (5.06 ± 1.75 vs. 6.40 ± 1.46 mU/l, p = 0.089, hp2 = 0.262). The homeostatic model assessment (HOMA2) of insulin sensitivity was decreased (156 ± 46 vs. 126 ± 30%, p = 0.057, hp2 = 0.316). Muscle markers of metabolic pathways were not significantly altered. Insulin signalling related GSK-3a/b phosphorylation was significantly reduced. CONCLUSION: Healthy sedentary subjects who were given a commonly consumed amount of energy drinks for 4 weeks, worsened their glucose homeostasis, fat oxidation and fat mass.