H1N1 influenza tends to cause high morbidity but low mortality (1% to 4%) Based on its wide spread, the World Health Organization (WHO) has declared the 2009 outbreak of the novel H1N1 flu a global pandemic. On April 27, 2009, health services in India were put on high alert to guard against the entry of the disease into India. Pathogenesis of an infection and treatment is a challenge to infection management worldwide. The aim is to study the pathogenesis of an infection and find out supplementary treatment. The study period was 15th August 2009 to 25th October 2009. In present study 30 positive cases of H1N1 influ-enza was included. 30 normal healthy persons as per IFCC guidelines were included as control subjects. In present study oxidative stress was assessed by estimating lipid peroxi-dation product in the form of thiobarbituric acid reactive substances [TBARS], antioxi-dants in the form of reduced glutathione and enzymatic antioxidants in the form of super-oxide dismutase [SOD] and glutathione peroxidase [GPx] of plasma. All the data were ana-lyzed by using the statistical package SPSS-10.0. Results are reported as mean plus/minus standard deviation. The plasma TBARS were significantly high but glutathione levels and SOD and GPx activity were significantly lowered in H1N1 influenza when compared with control subjects. The study show that increased LPO levels and decreased levels of glu-tathione and activity of antioxidant enzymes raise oxidative stress in H1N1 Influenza. Ele-vated oxidative stress may be playing a role in natural killer (NK) cell loss and play a role in pathogenesis of H1N1 influenza virus. The present study suggests that use of Tamiflu (oseltamivir) or Relenza (zanamivir) with supplementation of antioxidants can recovers H1N1 influenza earlier than only antiviral drugs therapy by increasing the levels of NK cells and help to protect H1N1 viral infection Key words: H1N1 Influenza, pathogenesis, oxidative stress, antioAuthor(s): Shashikant V. Nikam, Padmaja S. Nikam, M.R. Chandrashekar, S.T. Kalsad, Jnaneshwara K.B.