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An environment friendly and sustainable approach is being emerged in the area of nanotechnology for accelerated growth and development of culturable aquatic animals hence green chemistry is gaining momentum in recent years. The present study has been carried out to delineate the effects of selenium nanoparticles (Se-NPs) on growth performance, antioxidative status and immunity of fish reared under lead (Pb) and high temperature (34°C). Three hundred and fifteen fish were equally distributed in seven treatments in triplicates. Three isocaloric and isonitrogenous experimental diets viz. control (Se-NPs-0 mg/kg), Se-NPs at 1mg/kg and Se-NPs at 2mg/kg were formulated. The fish were reared under lead (Pb, 1/21st of LC50 (4ppm)) and high temperature (34°C) stress and fed with or without dietary Se-NPs. The effects of dietary Se-NPs were studied in terms of growth performance (Weight gain %, feed conversion ratio, protein efficiency ratio and specific growth rate), antioxidative status (catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase), neurotransmitter enzymes (AChE), stress biomarkers (heat shock protein 70, serum cortisol, blood glucose, vitamin C), immunological status (total protein, A/G ratio and respiratory burst activity) in Pangasinodon hypophthalmus post challenge with Aeromonas veronii biovar sobria. Results of the investigation demonstrated significant improvement of growth performance, antioxidative status, neurotransmitter enzyme activity, stress markers and more importantly enhanced immunity of the fish with dietary incorporation of Se-NPs at 1mg/kg. In addition, post bacterial infection, the relative % survival increased and cumulative mortality % decreased in the group fed with Se-NPs at 1mg/kg diet. Pb and high temperature treated and fed with control diet group showed devastating impact on the growth performance, antioxidative status, stress markers and immunity of the fish. Similarly, application of Se-NPs at 2mg/kg showed poor growth performance and elevated level of oxidative stress and other stress biomarkers including other biochemical attributes. Inclusive results indicated that, Se-NPs at 1mg/kg has capability to enhance overall performance and alleviate multiple stresses in P. hypophthalmus. Hence, Se-NPs at optimum level have ability to develop green chemistry in feed industry for better growth performance of the fish.Dietary Se-NPs enhanced growth performance and antioxidative status of Pangasinodon hypophthalmus reared under Pb and high temperature.Dietary Se-NPs protect neurotransmitter enzymes (AChE) of P. hypophthalmus reared under Pb and high temperature.Dietary Se-NPs enhanced Immunomodulation of P. hypophthalmus reared under Pb and high temperature.Dietary Se-NPs enhanced survival of P. hypophthalmus after infection with Aeromonas veronii biovar sobria.