Oseltamivir (Tamiflu) has been shown to be effective as a treatment and chemoprophylaxis for influenza virus infections. However, the safety consideration of oseltamivir should not be overlooked because adverse events associated with the drug have frequently been reported after the use of Tamiflu for the treatment of influenza patients. Here, we investigated oseltamivir´s influence on viral load, apoptosis, and cytokine response of influenza A H1N1-infected A549 or THP-1 cells. In addition, we analyzed the effect of the drug on the function of influenza-infected NK cells after oseltamivir treatment. The results of our study suggest that oseltamivir may inhibit both viral entry and release but may also enhance apoptosis of infected cells and interfere with NK cell function during influenza infection.