The aim of this study was carried out to evaluate the possible variation of hematological and biochemical profile in naturally infected cattle with Foot and Mouth Disease during the disease outbreak in 2016. For this purpose, a total number of 20 cattle over 1 year of age were used in this experiment. Of these 15 cattle showed characteristics clinical signs of FMD that exposed from 1 to 14 th days of post infection (DPI) and the remaining 5 cattle were clinically healthy and used as controls. Blood samples were used to establish total RBC, Hb, PCV, MCH and total MCV. Serum's samples were also collected and used to establish the total protein, albumin, globulin, blood urea nitrogen (BUN), cholesterol, calcium, phosphorus and glucose. The mean values of red blood cells (RBCs), and hemoglobin (Hb) were decreased significantly (p≤0.01), on the other hand MCV value was increased significantly (p≤0.05) in FMD affected cattle in comparison to their healthy group. The serum biochemical constituents were representing a significant reduction in the average value of total protein, albumin, globulin, blood urea nitrogen, cholesterol and significant production (p≤0.01) of phosphorus and glucose in cattle affected with FMD. Therefore, comparative study among the hematological and biochemical data concluded that, FMD causes significant decrease of RBC count, Hb, total protein, albumin, globulin, blood urea nitrogen, cholesterol and significant increase of MCV and glucose and phosphorus.