Oseltamivir is an influenza neuraminidase inhibitor that along with supportive therapy has shown to help critically ill patients infected with H7N9 and H1N1pdm influenza virus strains to recover from disease. The standard of care recommends the administration of oseltamivir via oral route which represents difficulties in patients with gastrointestinal complications. Here we tested the use of aerosol administration of oseltamivir to treat mice infected with influenza A/H7N9 virus or influenza A/H1N1pdm virus and directly compared this approach to the standard of care, oral administration. Using nose only delivery of aerosolized oseltamivir we observed a significant increase in efficacy of the treatment compared to oral administration characterized by reduced body weight loss, increased survival rate and dose sparing. The preclinical data presented here supports the possibility of using this approach in clinical settings.