Fifteen buffalo calves (145 ± 1.5 kg) for 180 days were randomly divided into three equal groups, CON, Az 12.5, and Az 25. The control group received the basal diet without supplements (CON). In the treatment groups, (Az 12.5) and (Az 25) we partially replaced crude protein in concentrate feed mixture with Azolla pinnata at rates of 12.5 and 25%, respectively. All diets were adjusted which contain 69% TDN and 16 % CP. Blood samples were collected during experiment and manure for digestion using the AIA. The results showed that substation protein of CFM with Azolla decreased (P<0.05) most nutrient digestibility and nutritive value in comparison with control group. Total protein and ALT were decreased (P<0.05) with the inclusion of Azolla at a rate of 25% of calves' diets when compared with the control group. The value of Albumin was higher at Az 12.5, while the value of globulin was increased with calves receiving 25% Azolla when compared control groups. The triglycerides concentration was lower (P< 0.05) with all Azolla groups than the control one.  The glucose, total protein, and albumin were higher (P< 0.05) at 180 days than 1 and 120 days.  However, the values of cholesterol, triglycerides, and creatinine were lower (P< 0.05) at 120 days than at 1 and 180. It could be concluded that the partial substitution of concentrate feed with Azolla pinnata by up to 25 % from protein of buffalo calve diets had no deleterious effects on growth performance, nutrient digestibility, and plasma constituents.