Chemical, electrophoretic and in vitro digestion methods were compared with respect to predictions given regarding fish meal (FM) quality. FMs were manufactured by mixing a press-cake, with spray dried stickwater concentrate from the identical raw material, thereby providing samples containing different quantities of water-soluble protein (wsp). A low-temperature-dried FM was employed as a reference. Acquired chemical data for each of the FMs included amino acid analysis and proximal composition (protein, fat, ash, ammonia, titration, salt, moisture). Biological methods in rat (net protein utilization, NPU, biological value, BV, and true digestibility, TD), capillary electrophoresis (sodium dodecyl sulphate-capillary gel electrophoresis, SDS-CGE)) and an in vitro enzymatic assay (trinitrobenzene sulphonic acid-based closed system with rainbow trout enzyme extract) were used for further comparisons with FM wsp content. A high correlation (R = 0.97; P < 0.001) between FM wsp content and titration volume was observed. In contrast to BV and NPU (R = 0.98; P < 0.001), TD (R = 0.2; P = 0.63) did not correlate with FM wsp. The peak area of a 50 kDa signal derived from SDS-CGE showed significant correlation (R = 0.98; P < 0.001) with wsp content. The fish-based in vitro system provided correlations with wsp content with respect to predigestion (R = 0.97; P < 0.0001) and post digestion (R = 0.77; P < 0.03) and for enzymatic liberation of amino groups as post digestion minus predigestion (R = 0.97; P < 0.0001) from the FM examined.