The inflammatory response of Atlantic cod (Gadus morhua L.) following vaccination with oil-based vaccines has not been previously characterized in any detail. In this study, groups of Atlantic cod were intraperitoneally injected with commercial oil-adjuvanted vaccines ALPHA JECT 3000 (AJ 3000) and AJ 6-2. A water-based vaccine ALPHA MARINE Vibrio (AVM), an experimental liposome vaccine and physiological saline (placebo) were also included for comparison. Histopathological changes at the injection sites were evaluated semi-quantitatively at 1, 2, 4, 8, 12, 16, 20 and 25 weeks post-vaccination (p.v.), parallel with the examination of vaccine antigen retention. Gross intra-abdominal lesions were only examined at 12 and 25 weeks. The results show that the onset of inflammation in all vaccinated groups was rapid to develop, with intense cellular infiltrations predominated by mononuclear cells especially in groups injected by oil-based vaccines. Inflammation induced by AVM and liposome vaccines resolved within 12 weeks. In contrast, oil-adjuvanted vaccines produced mild, persistent but ultimately decreasing reactions. Persistent antigens were observed in oil-based and liposome vaccines. The results show that the cod inflammatory response is similar to other bony fish species. The findings also suggest that cod has an efficient innate immune system that is able to rapidly remove or sequester antigens from the injection site leading to the down-regulation of inflammation. Oil-adjuvanted vaccines appear to be well-tolerated by this species and show promise as a possible approach for disease control.