Contrary to other preservation methods like thermal treatments, high pressure can destroy microorganisms without affecting the nutritional quality, color, or food texture. The firm texture of fish flesh is an important quality parameter. During the refrigerated storage, the tissue becomes softer and the muscle is deteriorated by different proteases. The aim of this study was to study the modification of the fish muscle proteins after high-pressure treatment during the refrigerated storage and to evaluate the effect of high-pressure treatment level on the post-mortem protein changes and enzyme activities. The calpain activity decreased with the high-pressure treatment and evolved differently during the refrigerated storage, depending on the level of pressurisation. Its inhibitor, the calpastatin was not affected by high pressure, but its inhibiting potential decreased during the post-mortem storage. The activities of cathepsins were modified by the high-pressure treatment and the time of storage, but depended according to their class. The electrophoresis profiles showed that sarcoplasmic proteins were modified according both the high-pressure treatment and the period of storage. For the myofibrillar proteins, the only changes were due to the high-pressure treatment.