The purpose of this study was to evaluate of acute phase response and oxidative damage in sheep naturally infected with Streptococcus pluranimalium using haptoglobin (Hp), nitric oxide (NO), and malondialdehyde (MDA) levels. The animal material of the study consisted of 60 sheep infected with S. pluranimalium (Infected group) aged between 4-6 years and 15 healthy sheep (Control group) aged 4-6 years old. Skin scrapings samples were obtained from infected sheep for microbiological analyses. Blood samples were taken from vena jugularis of animals in to vacuum tubes for biochemical analysis. From the samples taken from infected sheep, S. pluranimalium was identified by using VITEK 2 Compact Bacterial Identification and Monitoring System. Serum Hp and NO levels were determined by the spectrophotometric method and MDA levels were determined by the thiobarbituric acid (TBA) reaction. Hp (0.17±0.01 g/L), (P<0.001) MDA (1.67±0.04 μmol/L) and NO (31.14±1.61 μmol/L) (P<0.01) levels of the infected group were found to be significantly higher than the control group. It was concluded that high serum MDA and NO levels indicate that oxidative damage takes place in naturally infected sheep with S. pluranimalium. However, it can be assumed that higher Hp and low Alb concentrations might be an indicator of acute-phase response in the infected animals.