Immunostimulation by natural products, such as brown algae presents an alternative choice to antibiotics and vaccines in aquaculture. The present study was performed to determine the effects of dietary brown alga Padina pavonica onthebody composition measurements, antioxidant activity and innate immunity of Oreochromis niloticus before and after being challenged with Aeromonus hydrophila. The Nile tilapia (4.58 ± 0.03 g) samples were fed commercial pellets mixed with four concentrations of P. pavonica (2.0, 4.0, 6.0 and 8.0g/ kg) for 45 days under two different conditions: experimental (A) and farming (B). The results indicate that fish fed higher algal dose T4 (8.0g/kg) witnessed improved growth. All immunological parameters, including oxidative enzymes, somatic indices and lysozyme activities were assessed for both environments (A and B). The histological structure of the liver, spleen and intestine of fish showed some enhancements in treated group cells relative to the control fish. All groups after the feeding trials were challenged with the pathogenic bacteria Aeromonus hydrophila. No changes were detected in oxidative enzyme activities for both environments, while lysozyme activities recorded a reverse effect upon decreasing the higher algal dose subgroups T4. In addition, a decrease was recorded in the mortality rate in both environments after feeding with P. pavonica alga in all subgroups (10 and 20%), which indicates the defense effect of brown alga P. pavonica against the pathogenic bacteria.