The purpose of this study was to determine the effect of replacing fish meal, soybean meal, and con protein concentrate in an equal ratio with high protein distiller’s dried grains with yeast (HP50Y) on Pacific white shrimp growth, feed utilization efficiency, haemolymph parameters, and physiological gene expression . For eight weeks, a green water recirculation system was employed with a stocking density of 30 shrimp tank-1 (~38 shrimp m-2) and an initial weight of 0.22 ± 0.007 g (Mean Standard Deviation). Six distinct experimental diets were investigated. T he primary protein sources in the basal diet were sys tematically replaced (0-25% diet) with high protein distillers dried grains with yeast. In the study, no significant changes in shrimp growth indicators were found between shrimp reared on the various diets (p>0.05). We found no significant differences in feed utilization efficiency (p>0.05) except for net phosphorus retention (p<0.001 ). While physiological gene expression analysis is being investigated, the haemolymph index exhibited a similar pattern with no statistically significant outcome (p>0.05) . The results showed that, in the setting of natural productivity, different replacement levels did not impair the growth response, feed consumption, and haemolymph indicators of Pacific white shrimp when appropriately balanced with other protein sources. The results demonstrated the feasibility of replacing the primary protein source with high protein DDGS with yeast in practical feed applications. Overall, the use of high protein DDGS with yeast in shrimp feed formulation resulted in a good growth rate with no negative effects found.