Effect of different product formulation on the properties of resulting pomegranate seeds oil (PSO) microcapsules during spray drying encapsulation was studied. PSO microencapsulation was optimized using Box–Behnken's response surface methodology. Emulsion droplet size (3.01–9.21 µm) and viscosity (16–34 cP), product yield (50–76%), microencapsulation efficiency (76–88%), moisture (2.3–3.5 g/100 g dry matter), water activity (0.17–0.22), bulk density (262–522 kg/m3), hygroscopicity (14–23%), solubility (>97%), particle size (11.30–36.27 µm), and microstructure were analyzed. Three saturated and six unsaturated fatty acids were identified in the PSO; punicic acid was predominant in both unprocessed and microencapsulated ones. The ratio of saturated and unsaturated fatty acids was stable during processing, however, distribution of fatty acids – especially C18:3 isomers – changed by microencapsulation. Optimum product formula which simultaneously maximized the product yield and microencapsulation efficiency was predicted as 75.5 g/100 g emulsion dry matter (EDM) of maltodextrin/modified starch N-LOK (70/30), 24.5 g/100 g EDM of whey protein concentrate, and 15 g oil/100 g EDM. Peroxide and p-anisidine values of the encapsulated PSO were within acceptable range after spray drying. However, the oxidative stability decreased at high temperature (60°C) after 5 days of storage.