female's serum urea from Barrage region. For serum Fish serum reflects status of many biochemical processes in the metabolism. Many environmental stressors alter serum biochemical parameters in fishes. Thus, both sexes of Nile catfish, Clarias gariepinus, were collected from south (Al-Aiat) and north(Barrage) Cairo city to investigate the responses of serum gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), urea, uric acid and creatinine to environment in different seasons. Different seasonal patterns were reflected for serum biochemical parameters in all fish groups studied, Season significantly affected the serum ALP in all groups. Male's serum urea and uric acid from the two regions showed significant seasonal changes in addition to the female's serum urea from Barrage region. For serum creatinine, only females from Al-Aiat region demonstrated significant seasonal changes. Serum γ-GT did not show any significant seasonal change in this study. Location effect appeared more evident with serum ALP and urea and to lesser degree with serum creatinine. Serum γ-GT and uric acid were the lowest parameters affected with the location of samples. Serum γ-GT, ALP, urea and uric acid were affected by fish sex, while serum creatinine showed no significant sex change. All the serum biochemical parameters were affected by the interactions of season with location and season with both location and sex, while the interaction of location with sex affected only serum ALP and creatinine. No change was detected for the effect of season interaction with sex on the serum parameters.