Background and Aim. Increasing energy expenditure is an effective strategy for the prevention of obesity. In this respect, Lycium barbarum (goji berry) is of interest, as it has been shown to increase postprandial oxygen consumption. Although this suggests that energy expenditure was also increased, energy expenditure and substrate oxidation can only be assessed accurately when both oxygen consumption and carbon dioxide production are measured. We therefore investigated the effects of a single dose of Lycium barbarum fruit on postprandial energy expenditure and substrate oxidation in a randomized, double-blind crossover trial. In addition, markers of lipid and glucose metabolism were measured. Methods. Seventeen healthy, overweight men received in a random order a meal containing 25grams of dried Lycium barbarum fruit or a control meal matched for caloric content and macronutrient composition. Energy expenditure and the respiratory quotient were determined using indirect calorimetry before and up to 4hours after meal intake. Blood was sampled before and after meal intake at regular intervals for analyses of plasma glucose, serum triacylglycerol, and free fatty acid concentrations. Results. Energy expenditure significantly increased after the Lycium barbarum and control meal, but no differences were found between the meals (p=0.217). Postprandial changes in respiratory quotient (p=0.719) and concentrations of glucose (p=0.663), triacylglycerol (p=0.391), and free fatty acids (p=0.287) were also not affected by Lycium barbarum intake. Conclusions. A single dose of Lycium barbarum does not affect postprandial energy expenditure, substrate oxidation, and markers for lipid and glucose metabolism in healthy, overweight men.