Antibiotic resistance genes (ARGs) have become emerging contaminants through the overuse and misuse of antibiotics in animal agriculture. Propagation, development, and maintenance of such a contaminant through bacterial reservoirs are not well understood. Identifying environments to which ARGs are attenuated due to an inability to meet the metabolic burden of maintaining the plasmids that carry the ARGs, will give insight to possible solutions. An anaerobic environment was shown to cause the loss of tetracycline resistant (Tet R) gene TetC which is carried on the pSC101 plasmid within the tested strain Escherichia coli c600. Fluctuation and attenuation of the ARG harboring plasmid was also correlated with the intracellular reduction potential of the cells, which was measured as the NADH/NAD+ ratio. This suggests a relationship between ARG plasmid maintenance and the energy state of the cells, possibly reflecting that the energy burden of ARG and associated plasmid maintenance is more difficult to meet under anaerobic conditions that are less favorable from an energy harvesting perspective. These results suggest that the use of anaerobic barriers (e.g., permeable anaerobic mulch barriers or anaerobic lagoons) to intercept ARG-laden drainage from confined animal feeding operations may attenuate the propagation of ARGs into the environment.