The pandemic influenza A virus (H1N1) was transmitted to the human population since 2009, resulting in some consequences of viral pneumonia, respiratory failure, multiple organ failure and, most severely, death. In clinical practice, Chinese medicine possessed extensive experience for prevention and treatment of influenza, but its mechanism still remain unclear. In addition, the efficacy of combination therapy of Chinese and Western medicine was attractive, but not yet clear. In the present study, 131 patients from Guangzhou China referred for H1N1 virus mRNA testing for the evaluation of possible influenza A-infected were eligible for participation. A metabonomics study was carried out to explore the difference between before and after treatment in patients with H1N1 through Chinese and/or Western medicine. Results from metabolic profiling and biochemical detection indicated significant metabolic change in the arachidonic acid metabolic pathway. In the group of combination therapy of Chinese and western medicine, its efficacy was best and the potential biomarkers were significantly changed compared with untreated state. Those results indicated that the potential metabolic biomarker could be supplemented with biochemical detection to obtain more precise diagnosis for H1N1 infection. Clinical trials registration: Clinical Trials. Gov No. 2008GL-50 (C) 2012 Elsevier B.V. All rights reserved.