Serum levels of volatile organic compounds (VOCs) are increasingly being measured in people as part of exposure investigations designed to assess potential environmental exposures. Given the breadth of VOC sources, it is essential to have an understanding of typical background levels found in people. Data from the National Health and Nutrition Evaluation Survey (NHANES) provide information on serum levels of many compounds in the general U.S. population, so it is useful for characterizing background levels. As such, the objective of this analysis was to derive serum reference values for the U.S. population using the 2003-2004 NHANES dataset. Weighted summary statistics were developed for 21 VOCs commonly measured in community exposure investigations, and stratified by smoking status and other relevant demographic variables (gender, age and ethnicity). Of the 21 VOCs evaluated, 12 were found to be non-detect in all samples: 1,1,2- trichloroethane, 1,1-dichloroethane, 1,1-dichloroethene, 1,2-dibromo-3-chloropropane, 1,2—dichlorobenzene, 1,2-dichloroethane, 1,2-dichloropropane, 1,3- dichlorobenzene, chlorobenzene, cis-1,2-dichloroethene, hexachloroethane and trans-1,2-dichloroethene. Six of the remaining VOCs (1,1,1-trichloroethane, 1,1,2,2-tetrachloroethane, carbon tetrachloride, dibromomethane, methylene chloride and trichloroethene) had detection frequencies less than 2% and thus the mean and 95th percentile serum levels were very near or at the LOD/√2. Only 3 VOCs had detection frequencies greater than 15‰. The mean and 95th percentile concentrations, respectively, for these compounds were: 0.91 and 3.17 ng/ml for 1,4- dichlorobenzene, 0.04 and 0.12 ng/ml for styrene, and 0.08 and 0.14 ng/ml for tetrachloroethene. Only styrene had significantly elevated mean and median serum levels among smokers, regardless of smoking biomarker. The concentrations of other VOCs were not impacted by smoking status or demographics. These summary statistics provide a critical reference tool for assessing potential exposure to VOCs, as well as identifying potential populations of concern.