A higher prevalence of Campylobacter concisus and higher levels of IgG antibodies specific to C. concisus in Crohn's disease patients than in controls were recently detected. In this study, 1D and 2D gel electrophoresis coupled with LTQ FT-MS and QStar tandem MS, respectively, were performed to characterize the secretome of a C. concisus strain isolated from a Crohn's disease patient. Two hundred and one secreted proteins were identified, of which 86 were bioinformatically predicted to be secreted. Searches were performed on the genome of C. concisus strain 13826, and 25 genes that have been associated with virulence or colonization in other organisms were identified. The zonula occludens toxin was found only in C. concisus among the Campylobacterales, although expanded searches revealed that this protein was present in two epsilon-proteobacterial species from extreme marine environments. Alignments and structural threading indicated that this toxin shared features with that of other virulent pathogens, including Neisseria meningitidis and Vibrio cholerae. Further comparative analyses identified several associations between the secretome of C. consisus and putative virulence factors of this bacterium. This study has identified several factors putatively associated with disease outcome, suggesting that C. concisus is a pathogen of the gastrointestinal tract.