Short chain fatty acids (SCFAs), produced from fermentation of dietary fibre by the gut microbiota, have been suggested to modulate energy metabolism. Previous work using rodent models have demonstrated that oral supplementation of the SCFA propionate raises resting energy expenditure (REE) by promoting lipid oxidation. The objective of this study was to investigate the effects of oral sodium propionate on REE and substrate metabolism in humans. Eighteen healthy volunteers (9 females and 9 males; Age: 25±1 y; Body Mass Index: 24.1±1.2 kg/m2) completed two study visits following an overnight fast. Tablets containing a total of 6845mg sodium propionate or 4164mg sodium chloride were provided over the 180 min study period in a random order. REE and substrate oxidation was assessed by indirect calorimetry. Oral sodium propionate administration increased REE (0.045±0.020 kcal/min; P=0.036) accompanied with elevated rates of whole-body lipid oxidation (0.012 ± 0.006 g/min; P=0.048) and independent of changes in glucose and insulin concentrations. Future studies are warranted to determine whether the acute effects of oral sodium propionate on REE translate into positive improvements in long-term energy balance in humans