The present study was planned to investigate the clinicoplathological and histopathological changes on the blood of catfish (Clarias gariepinus) infected with Pseudomonas florescence. A total number of 240 catfish were collected from Ismailia channel and subdivided to 4 groups 60 for each: the control group, infected group, β-glucan group and β-glucan infected group. The blood samples were taken at 1, 3 and 5 weeks for hematological and biochemical examinations. Tissue samples from spleen, liver, kidney and gills were taken for histopathological techniques. The hematological results revealed significant decrease of RBCs count, Hb concentration and PCV% with significant increase of T.L.C, heterophils and lymphocytes of the infected group compared to the control group. The β-glucan groups showed significant increase of RBCs count, Hb and PCV% with significant increase of T.L.C, heterophils, lymphocytes and monocytes. Serum biochemical results showed marked elevation in ALT, AST, urea, creatinine, uric acid and glucose of the infected group. While, β-glucan improved the liver function, kidney function tests and glucose before and after the infection compared to the control group. The challenge test revealed a significant lower mortality percentage in the group received β-glucan supplemented diets. Histopathologically, marked degenerative changes and necrosis were evident in the infected group. While, β-glucan groups showed hyperactivity of melenomacrophage centers of haemopiotic organs. It could be concluded that β-glucan acts as a dietary supplement.