The population of the Chilean endemic marine gastropod Concholepas concholepas locally called “loco” has dramatically decreased in the past 50 years as a result of intense activity of local fisheries and high environmental variability observed along the Chilean coast, including episodes of hypoxia, changes in sea surface temperature, ocean acidification and diseases. In this study, we set out to explore the molecular basis of C. concholepas to cope with biotic stressors such as exposure to the pathogenic bacterium Vibrio anguillarum. Here, 454pyrosequencing was conducted and 61 transcripts related to the immune response in this muricid species were identified. Among these, the expression of six genes (CcNFκβ, CcIκβ, CcLITAF, CcTLR, CcCas8 and CcCath) involved in the regulation of inflammatory, apoptotic and immune processes upon stimuli, were evaluated during the first 33 h post challenge (hpc). The results showed that CcTLR, CcCas8 and CcCath have an initial response at 4 hpc, evidencing an up-regulation from 4 to 24 hpc. Notably, the response of CcNFKB occurred 2 h later with a statistically significant up-regulation at 6 hpc and 10 hpc. Furthermore, the challenge with V. anguillarum induced a statistically significant down-regulation of CcIKB between 2 and 10 hpc as well as a down-regulation of CcLITAF between 2 and 4 hpc followed in both cases by an up-regulation between 24 and 33 hpc. This work describes the first transcriptomic effort to characterize the immune response of C. concholepas and constitutes a valuable transcriptomic resource for future efforts to develop sustainable aquaculture and conservations tools for this endemic marine snail species.