Comparison of the concentrations of serum nitric oxide; malonaldhyde; total protein and its electrophoretical profile in Nile catfish Clarias lazera after supplementation with probiotic for 45 days either 1 time/week (W1) all over the experiment or 3 times/week for the 1st two weeks then 1 time/week till the end of the experiment (W3) were investigated. Probiotic supplementation affects on both serum nitric oxide and malonaldhyde. No effect of probiotic supplementation on serum total protein. Twelve fractions were resolved of which 10 and 11 were the maximum numbers that appeared with consistency in females and males respectively. Polymorphism appeared in both males and females of the initial; control; W1 and W3 groups. Probiotic feeding altered the relative density of resolved serum protein fractions. In both W1 and W3 groups, the 9th fraction recorded higher values in both sexes, while fractions # 10 and 11 (in γ-globulin area) recorded lower values in both sexes. The relative densities of fractions # 5; 7 and 9-12 were significantly affected by probiotic supplementation. Our study indicated that probiotic supplementation to fish diet is not a long-term effect and preferred to be added periodically according to farm management.