Vibrio anguillarum is a marine bacterium that can cause vibriosis in many fish and shellfish species. Although phage therapy has been proposed as an alternative treatment, the defense mechanisms against phage infection in V. anguillarum and their impact on host function are not fully understood. Here, we examined phage defense strategies in four V. anguillarum strains during exposure to the broad-host-range bacteriophage KVP40.