This experiment aimed to appraise growth performance, hematological and immuno-physiological indices of Nile tilapia when fed on diets in which soybeans were partially replaced by Azolla pinnata or Nannochloropsis oculata. A control diet (basic diet) was tested against 6 practical diets (3 diets partially replaced soybean with Azolla pinnata and 3 diets partially replaced soybean with Nannochloropsis oculata at three different percentages (2.5, 5 and 7.5 %) The highest values of growth parameters were recorded in T3 (Azolla 5 %), followed by T4 (Azolla 7.5 %), T5 (Nano 2.5 %), T7 (Nano 7.5 %), T6 (Nano 5 %), T2 (Azolla 2.5 %), and then T1 (negative control). At the end of the experiment, T4 recoded the highest values of Total protein and Globulin while the lowest readings were in T3, Albumin lowest value was in T5 and the highest one accomplished in T2 with a significant differences between all treatments. For the antioxidant parameters, the negative control (T1) recoded the highest MDA value, while had the lowest values of SOD, GPX and Lysozyme. The highest values of (SOD and GPX) accomplished in T6 while the highest value of Lysozyme was recorded in T4. The challenge with A. hydrophila showed that, the highest mortality rate (80 %) was recorded in control, while the lowest one (10 %) was recorded in T3 and T4.