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Moringa oleifera is one of the most promising plants in aquaculture because it improves the health status, zootechnical parameters and resistance against diseases. This research evaluates the physicochemical, antioxidant values of spray-dried Moringa oleifera seed extract microencapsulates obtained at 140 and 180 °C with whey protein concentrate (WPC) and maltodextrin (MD) as wall materials in two different proportions: WPC 100% and WPC-MD (3:1). Also, immune response of peripheral blood leukocytes (PBL) of Longfin yellowtail Seriola rivoliana stimulated with spray-dried Moringa oleifera seed for 24 h was assessed. The physicochemical parameters show that the recovery yield for all the treatments was of 65% and microencapsulates demonstrated to be stable in the physicochemical tests with low solubilization times and protection against humidity. For WPC-MD (3:1)/140 °C, bioactive compound retention and antioxidant potential were higher than in other combinations. The immunological test show that any treatments was non-cytotoxic against peripheral blood leukocytes. WPC-MD (3:1)/140 °C treatment enhanced immune parameters as phagocytosis, respiratory burst, myeloperoxidase activities and nitric oxide production. Immune related genes as IL-1β and TNF-α were up-regulated in those stimulated leukocytes with WPC-MD (3:1)/140 °C. The results suggest that this combination may be a good alternative for animal health as a medicinal and immunostimulant additive., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)