The limit of tolerance to salinity in freshwater fish has become an important environmental factor influencing growth performance. Therefore, this study aimed to explore the impact of different levels of salinity on behavioural responses, growth performance, haematological, oxidative and biochemical stress parameters, in addition to immune parameters of African catfish. Three‐hundred and Sixty juvenile African catfish were randomly distributed into six groups and exposed to different salinity levels (0, 4, 8, 12, 16 and 20 ppt) with three replicate tanks per treatment group; each tank contained 20 individuals for 42 days. Behavioural responses of fish were monitored during the experimental period. Growth performance, haematological, oxidative and biochemical stress parameters, in addition to immune parameters and osmotic pressure, were also determined at the end of the treatment period. Results revealed that the proportion of fish performing abnormal stress behavioural responses increased directly to the salinity level. In contrast, the survival rate and growth performance were decreased with high feed conversion at the higher salinities. Inconsistent, the haematological, oxidative, biochemical, immune and osmotic pressure parameters were altered gradually with the increase in the salinity level. Therefore, salinity level could influence the African catfish's behaviour, survival and growth when they exceed the tolerance limit.