The climatic conditions in saltern saline environments allows the growth of microorganisms adapted to these peculiar ambient and could represent a promising source of new bioactive compounds that could have applications on as animal food supplements, including aquaculture. In this study, we evaluated the role of Yarrowia lipolytica N-6 isolate, from a hypersaline natural environment (Guerrero Negro, Baja California Sur, Mexico), as immunostimulant of the non-specific immune response of head-kidney and spleen Pacific red snapper (Lutjanus peru) leukocytes after challenge with Vibrio parahaemolyticus. In this study, the presence of Y. lipolytica reduced considerably the V. parahaemolyticus load in spleen leukocytes. In vitro assays using head-kidney and spleen leukocytes showed that the response to V. parahaemolyticus infection reveled that leukocyte pre-incubated with Y. lipolytica N-6 significantly increased the non-specific immune response such as respiratory burst, phagocytic activity, NO and MPO activities follow by an increase in SOD and CAT activities, and at the same time inhibited leukocyte apoptosis caused by V. parahaemolyticus. Moreover, Y. lipolytica N-6 incubation also regulated the transcription of genes related to immunity (IL-1β) or oxidative stress (MnSOD, icCu/ZnSOD or CAT) in leukocytes. These results strongly support the idea that the extreme yeast Y. lipolytica N-6 isolate can stimulate the non-specific immune parameters and the antioxidant immune mechanism in head-kidney and spleen Pacific red snapper leukocytes and could be used as potential immunostimulant.