A feeding trial was performed to evaluate the efficacy of Dietary Nucleotides (Nucleoforce™) on Growth performance, haematological, biochemical, Immunological indices and disease resistance of Pangasianodon hypophthalmus fish to Pseudomonas aeruginosa. Dietary nucleotides were incorporated in the diet at different concentrations; group I control, group II 250 g/ ton diet and group III 500 g/ ton diet for 8 weeks. At the end of the feeding trial, weight gain, and specific growth rate (SGR) were recorded. Results showed that there was a significant increase in fish groups received diet supplemented with nucleotides in comparison with the control group. Haematogram indices showed a significant elevation in RBCs count, HB value, WBCs, and leukocytic count. Biochemically, High superoxide dismutase (SOD) activity, total protein and globulin levels were recorded in fish fed on 500g/t nucleotide (NT). Immunologically, Lymphocytic proliferation activity, Nitric oxide concentration and Serum lysozyme activity were continuously increased in 250g/t and the 500g/t NT treatment groups along feeding duration. At the end of 8^th week, the experimentally reared fish were challenged intraperitoneally with virulent strain of Pseudomonas aeruginosa (0.2 ml of 3× 10⁷ CFU)  and the cumulative mortalities  were recorded to be  lower in nucleotide supplemented groups compared to the control group. In conclusion, the supplementation of fish diet with  nucleotides in concentration of  500g/t nucleotide can improve the general health status of P. hypophthalmus via increasing the disease resistance and minimizing stressful conditions.