Nonspecific anti-inflammatory drugs have been purported to reduce the burden of severe influenza disease. We demonstrate that, unlike oseltamivir administration, simvastatin administration did not reduce morbidity, mortality, or viral load of mice infected with H1N1 or H5N1 viruses. No added benefit to the efficacy of oseltamivir therapy was observed when mice were treated in combination with simvastatin. Modest reductions in lung cytokine production in H5N1 but not H1N1 virus-infected simvastatin-treated mice indicate a potential benefit for statin use in mitigating disease following severe virus infection. © 2013 .