The lumpfish, Cyclopterus lumpus L. is an emerging and most promising aquaculture fish currently used for a biological control against sea lice in salmonids. However, the lumpfish is prone to a number of bacterial diseases including vibriosis, atypical furunculosis and pasteurellosis. The use of vaccines in aquaculture has been one of the best prophylactic measures against fish bacterial diseases; vaccines can protect the lumpfish from bacterial diseases. Thus, it is essential to investigate the adaptive humoral immune response of the lumpfish in order to develop protective vaccines against the bacterial diseases. This work is the first to study the adaptive humoral immune response of the lumpfish in response to immunization with formalin inactivated whole bacteria (WB) antigens and challenge with different Gram-negative bacteria after vaccination or without vaccination. Immunization was conducted against two atypical A. salmonicida, V. anguillarum O2, Pasteurella spp. and V. ordalii. Analysis of the different lumpfish antisera using sonicated WB antigens by ELISA and western blot revealed the presence of strong specific or cross-reactive antibodies two weeks post immunization. The antisera to both atypical A. salmonicida strains had antibodies that detected common antigenic components directed to ca. 10, 13, 20, 22, 28, 50 and 55 kDa proteins. However, antibodies to one of the atypical strains (8546) did not recognize the 50-kDa protein from the heterogeneous antigen (AL20460) on the western blot. The absence of the 50-kDa protein in one of the atypical A. salmonicida may contribute to differences in the level of specific antibody response. Antibodies to strain AL122 (V. anguillarum O2) reacted strongly with a 14-kDa antigenic component of heterogeneous antigens from strains 8752 (V. anguillarum O1) and strain 8657 (V. ordalii). The Pasteurella spp. induced the highest level of antibodies directed to 100 and 20 kDa proteins of a homogeneous antigen. Moreover, antibodies to Pasteurella spp. reacted with 100, 73, 37 and 20 kDa protein components of a heterogeneous antigen from P. skyensis. However, V. ordalii induced the lowest antibody response; no specific antibodies were detected in antisera to V. ordalii by the western blot analysis. The lumpfish’s specific humoral immune system showed strong antibody response to vaccination post challenge (i.p.) with strains 8546 (atypical A. salmonicida), AL20460 (atypical A. salmonicida), 8752 (V. anguillarum) and Pasteurella spp. The trivalent and the commercial AMM3 vaccines against atypical furunculosis showed higher antibody levels after challenge with strain 8546 (atypical A. salmonicida) than challenge with strain AL20460 (atypical A. salmonicida). The monovalent vaccines had similar effect on antibody levels after challenging with either of the atypical A. salmonicida strains. The trivalent and monovalent vaccines against Vibriosis induced similar amount of antibodies post challenge with strain 8752 (V. anguillarum). However, the non-vaccinated groups, in general, displayed low antibody levels post challenge with post challenge with strains of the atypical A. salmonicida, 8752 (V. anguillarum O1), and Pasteurella spp. by any of the challenge exposures (bath, i.p., or cohabitation). These results indicate that the use of the vaccines in the lumpfish may play a protective role against some of the bacterial diseases; however, further studies are needed. Moreover, total serum IgM in the lumpfish was quantified by single radial immunodiffusion assay. The mean total IgM (mg/ml) post immunization for the different groups was estimated at the range of 1.02 to 0.41 mg/ml, which is in the range also found in other fish species. Master i Havbruksbiologi - Generell havbruksbiologi MAMN-HAV HAV399