We have investigated the plasma proteome by using 2D gel electrophoresis and MS from patients with severe acute respiratory syndrome (SARS). A complete proteomic analysis was performed on four patients with SARS in different time courses, and a total of 38 differential spots were selected for protein identification. Most of the proteins identified are acute phase proteins, and their presence represents the consequence of serial cascades initiated by SARS-coronavirus infection. There are several proteins that have never been identified in plasma before using 2D gel electrophoresis, among which peroxiredoxin II was chosen for further study by analyzing additional 20 plasma samples from patients with probable and suspected SARS and patients with fever, respectively. The results showed that the level of plasma peroxiredoxin II in patients with SARS is significantly high and could be secreted by T cells. Taken together, our findings indicate that active innate immune responses, along with the oxidation-associated injuries, may play a major role in the pathogenesis of SARS.