The gram-negative bacterium Vibrio (Listonella) anguillarum is the causative agent of vibriosis, a bacterial disease affecting aquacultural industry across the globe. The full mechanism of V. anguillarum pathogenesis is not completely understood, but many virulence determinants have been identified. The current study aimed to obtain molecular insights into the proteome response of the bacterium to several conditions mimicking vibriosis. Our data shed light on the adaptability of V. anguillarum to oxidative stress, iron limitations and the complement system, and offer potential virulence determinants associated in particular with septicemia over the course of vibriosis.