The mucus protein profile of Atlantic salmon (Salmo salar) and changes due to infection with sea lice (Lepeophtheirus salmonis) were examined. Two-dimensional gel electrophoresis was performed on salmon skin mucus and comparisons between control and infected fish mucus were made. LC MS/MS identified intracellular proteins, calmodulin, actin, and hemopexin and plasma proteins, such as apolipoproteins, lectin, plasminogen and transferrin. Plasma proteins in the mucus may result from either direct expression by epidermal cells, leakage of plasma or via a secondary circulation system. Therefore, RT-PCR was used to measure mRNA of transferrin and lectin in Atlantic salmon skin. Transferrin expression was observed suggesting direct expression by the epidermis. Lectin expression was not detected suggesting another mechanism of entry into mucus, either leakage from plasma or secondary circulation. The lack of observable albumin on 2D gels, suggests that mucus lectin may arise from the secondary circulation route. Interestingly, ?-actin was a significant component of Atlantic salmon mucus. Cleaved actin and transferrin fragments were observed and positively correlated with sea lice infection suggestive of proteolytic activity. Increased levels of cleaved transferrin during sea lice infection may activate the nitrous oxide response of salmon macrophages, as part of the fish's immune response to sea lice infection.