Lumpfish (Cyclopterus lumpus), a native fish of the North Atlantic Ocean, is utilized as cleaner fish to biocontrol sea lice infestations in Atlantic salmon aquaculture. However, bacterial infections are affecting cleaner fish performance. Vibrio anguillarum, the aetiological agent of vibriosis, is one of the most frequent bacterial infections in lumpfish, and effective vaccine programmes against this pathogen have been identified as a high priority for lumpfish. Vibrogen-2 is a commercial polyvalent bath vaccine that contains formalin-inactivated cultures of V. anguillarum serotypes O1 and O2, and Vibrio ordalii. In this study, we evaluated Vibrogen-2 efficacy in lumpfish against a local isolated V. anguillarum strain. Two groups of 125 lumpfish were bath-immunized, bath-boost-immunized at four weeks post-primary immunization, and intraperitoneally (i.p.) boost-immunized at eight weeks post-primary immunization. The control groups were i.p. mock-immunized with PBS. Twenty-seven weeks post-primary immunization, the fish were i.p. challenged with 10 or 100 times the V. anguillarum J360 LD50 dose. After the challenge, survival was monitored daily, and samples of tissues were collected at ten days post-challenge. Commercial vaccine Vibrogen-2 reduced V. anguillarum tissue colonization and delayed mortality but did not confer immune protection to C. lumpus against the V. anguillarum i.p. challenge.