The current experiment was conducted to spot light on the impact of thermal heat stress on the susceptibility of Nile tilapia to Aeromonas hydrophila infection. Four different groups of Nile tilapia (Oreochromis spp.) were used as follows: the first and the second groups were exposed to sudden rising of the water temperature up to (Upper Critical Limit UCL] (37-40°C) and by the end of the 48 hours the Ist group was challenged with A.hydrophila. The third group was kept under normal temperature (19-21°C) (comfort zone), and by the end of the 48 hr it was challenged with the for mentioned Bactria. The forth group was held as control under normal temperature, clinical signs, PM lesions and case fatality % were recorded for both the heat stressed fish and the challenged group.Whole citrated blood samples were collected in successive timing intervals from each group separately, namely, | hr., 24 hr. 48 hr and 72 hr. post heat stress. Some biochemical parameters were measured as glucose, total protein, and cortisols. Blood films were prepared to calculate the Heterophil, Lymphocyte, (H/ L ratio). The histopathological features of the different organs of the heat stressed Nile tilapia were discussed It was found that fish under warm-water stress at (UCL) 37-40°C suffered from abnormal behaviors; expressed obvious clinical signs as well as increased mortalities .PM recorded severe congestion in internal organs. The plasma glucose increased directly post stress then declined till 48 hours. Values of Plasma cortisols and total plasma protein (TPP) of stressed fish were varied along the curse of the experiment. The histopathological features of internal organs