The aim of the present study was to assess the comparative changes of the selected acute phase proteins (APPs) and immunoglobulins in buffalo and bovine calves with respiratory disease. A total of 65 calves (28 buffalo and 37 bovine) were studied. Of all, 45 calves (21 buffalo and 24 bovine) were diagnosed to have respiratory disease. In addition, 20 clinically healthy calves were randomly selected as a control group (7 buffalo and 13 bovine). Blood samples were collected to get complete blood count and to measure APPs and immunoglobulins. In buffalo calves, the clinical index scores were decreased significantly (p < 0.05) than bovine ones, especially in acute respiratory disease. Fibrinogen and Haptoglobin levels were increased significantly (p < 0.05) in acute respiratory diseases compared with chronic cases. In acute respiratory disease, buffalo calves had significant higher levels (p < 0.05) of Hp and IgG than in bovine one. In both buffalo and bovine calves, IgA and IgG levels showed a significant decrease (p < 0.05) in acute respiratory diseases compared with chronic. However, total protein and globulin levels showed a significant decrease (p < 0.05) in calves with chronic respiratory diseases. Conversely, albumin level showed a significant (p < 0.05) decrease in acute disease only. This is the first report describes the APPs in buffalo calves with respiratory disease. The variation of Hp and IgG in buffalo calves than bovine may suggest species difference. Further studies need to be done on experimental respiratory infection in buffalo calves to establish outstanding data about acute phase response. Statistics