As little is known about the oxidant/antioxidant status in buffalo with ketosis, the present study was delineated to assess the oxidative stress level associated with clinical ketosis in water buffalo. A total of 91 parturient buffalo at smallholder farms were studied (61 suspected to be ketotic and 30 healthy). Clinical and biochemical investigations were carried out for each buffalo. Based on clinical findings and the level of beta-hydroxybutyrate (BHB), buffalo were allocated into ketotic (42), subclinical cases (19). Clinically, there was an association between clinical ketosis and anorexia (p<0.001), constipation (p<0.001), decreased milk yield (p<0.001), ruminal stasis (p<0.001), and loss of body condition (p<0.01). Biochemically, in clinical ketosis compared with subclinical and control cases, there was a significant increase (p<0.05) of BHB, malondialdehyde (MDA), nitric oxide (NO), aspartate aminotransferase (AST), L-alanine aminotransferase (ALT). However, there was a significant decrease of glucose, phosphorus, magnesium,total cholesterol and HDL-cholesterol. There was a positive correlation between BHB and MDA (r=0.433), BHB and NO (r=0.37), MDA and NO (r=0.515), and Glucose and phosphorus(r=0.521). However, there was a negative correlation between BHB and glucose (r= -0.341) and HDL and NO (r= -0.379). The result of the present study indicates that hyperketonemia in buffalo is associated with an increase of oxidative stress levels. Further studies need to be done on the efficacy of antioxidants as an ancillary treatment to relief the oxidative stress caused by ketosis.