Exposure to inorganic arsenic (iAs) in drinking water remains a global issue of concern and is associated with a range of health outcomes, including immune dysfunction. Young children have been identified as a particularly sensitive population, yet mechanisms of adverse health outcomes are understudied. Here we set out to examine the effects of iAs exposure on circulating serum proteins in adolescents. To identify proteins as potential indicators of disease, levels of total urinary arsenic (U-tAs) and its methylated metabolites were determined and serum proteins assessed for differences in expression. The results indicate an enrichment of TNF-regulated immune and inflammatory response proteins that display decreased expression levels in relation to increasing U-tAs. Notably, when analyzed in the context of the arsenical proportions, there was minimal overlap between the protein lists, with the most robust response observed in relation to %MMAs. These data represent the first assessment of protein expression in serum in adolescents exposed to inorganic arsenic.