Killing activity of fresh Oreochromis niloticus serum was used as an indicator of the natural immunity. Serum killing activity was tested in temperature stressed fish exposed to 32 ±1°C to different Pseudomonas fluorescens strains. As a clinical estimate of natural immunity and disease resistance, experimental challenge with P. fluorescens strains was conducted. The results cleared that serum killing activity at 32±1°C was almost stopped where fish got infected after bacterial challenge. On the other hand, control fish group kept at 23± 1°C developed serum killing activity and resistance to the acquisition of infection after challenge. A correlation was found between resistance activities of P. fluorescens strains to serum killing and their corresponding courses of infection after bacterial challenge. However, the results of experimental challenge conducted at 32±1°C suggested that the immunocompromising state resulted from the stress of inability to withstand high water temperature is exclusively the critical aspect for the induction of infection.