The main objective of this study was to increase the knowledge about the mucosal immunity of Salmo salar, using soybean meal-induced enteritis as a model of inflammation. A control fish meal (FM) and a diet containing 20% soybean meal (SBM) were fed to salmon for seven weeks in seawater. There was no growth difference between groups. However, histology of distal intestine (DI) showed a mild inflammation in the fish fed SBM. Proteomic results revealed differences between the diets. Among the proteins detected uniquely in DI mucus of SBM group, complement C5, Galectin and Glutathione synthetase are involved in innate and adaptive immunity, inflammation, redox signalling and detoxification of xenobiotics in mammals, and similar roles are hypothesized in salmon. Adenylosuccinate synthetase and putative aminopeptidase were uniquely detected in the skin mucus of SBM group. Trypsin enzymatic activity was significantly decreased in the DI of SBM group. Significantly higher production of immunoglobulin M and Mucin-like protein in DI mucus in SBM group was observed, while an increase in immunoglobulin D and lysozyme but decrease in chymotrypsin was detected in the skin mucus of the same group. We propose mucosal immunoglobulins as diagnostic biomarkers for assessment of novel feed ingredients and aquafeeds.