The development of superior tools for molecular and computational biology in recent years has provided an opportunity for the creation of faster toxicological screens that are relevant for, but do not rely on, mammalian systems. In this study, NMR spectroscopy and GC-MS based metabolomics have been used in conjunction with multivariate statistics to examine the metabolic changes in the nematode Caenorhabditis elegans following exposure to different concentrations of the heavy metal nickel, the pesticide chlorpyrifos, and their mixture. Novel metabolic profiles were associated with both exposure and dose level. The biochemical responses were more closely matched when exposure was at the same effect level, even for different chemicals, than when exposure was for different levels of the same chemical (e.g., low versus high dose). Responses to the mixture reflected the contribution of the chemicals to the overall exposure. In common with the metabolic responses of several other species exposed to the same chemicals, we observed changes in branch chain amino acids and tricarboxylic acid cycle intermediates. These results form the basis for a rapid and economically viable toxicity test that defines the molecular effects of pollution/toxicant exposure in a manner that is relevant to higher vertebrates.