Abstract: Background and Objective: In oil refining process, lipase-catalyzed de-acidification is a promising alternative to conventional neutralization. The enzymatic esterification of free fatty acids in crude sardine oil was carried out by immobilized lipase novozymes 435. The aim of this study was to upgrade the sardine oil processed in Morocco by using enzymatic solutions and to investigate the effect of the various parameters involved in enzymatic deacidification of fish oil: Pressure, ratio of oil/novozymes 435, ratio of oil/glycerol, temperature. Materials and Methods: The enzymatic deacidification optimization was performed with novozymes 435, by using two oils with different initial acidity. The results obtained in the present study were analyzed through two-way ANOVA test. Results: The greater deacidification yields were obtained with: A temperature of 70°C, a ratio oil/glycerol: 2%, a ratio oil/novozyme 435: 1%, a pressure: 15-25 mbar. Conclusion: From an industrial point of view, this eco-friend enzymatic solution may allow Moroccan fish oil producers to achieve acid number values that meet the standard.