Significant food-borne disease outbreaks have occurred from consumption of ready-to-eat foods, including produce, contaminated with Listeria monocytogenes. Challenging food matrices (e.g., cantaloupe, sprouts) with limited processing steps postharvest to reduce pathogen loads have underscored a need for new mitigation strategies. Chlorine dioxide (ClO 2 ) is increasingly being used in produce and other food systems to reduce food-borne pathogen levels. The goal of this study was to characterize the transcriptional response and survival of L. monocytogenes 10403S exposed to ClO 2 . The transcriptional profile of log-phase cells exposed to 300 mg/liter ClO 2 for 15 min was defined by whole-genome microarray. A total of 340 genes were significantly differentially expressed. Among the differentially expressed genes, 223 were upregulated (fold change > 1.5; adjusted P value < 0.05) in role categories responsible for protein fate, cellular processes, and energy metabolism. There were 113 and 16 genes differentially expressed belonging to regulatory networks of B and CtsR, respectively. We assessed L. monocytogenes 10403S survival after exposure to 100, 300, and 500 mg/liter aqueous ClO 2 in brain heart infusion (BHI) broth; there was a significant difference between cells exposed to 500 mg/liter ClO 2 and those exposed to all other conditions over time (P value < 0.05). Isogenic ⌬sigB and ⌬ctsR mutants exposed to 300 mg/liter ClO 2 were more sensitive to ClO 2 than the wild type under the same conditions. These results provide an initial insight into the mechanisms that L. monocytogenes employs to survive sublethal ClO 2 and further our understanding of the inactivation mechanisms of this increasingly used sanitizer.