Influenza virus contributes substantially to the global human and animal disease burden. To protect individuals against disease, strategies are needed to minimize the time an individual is at risk of developing disease symptoms. Passive immunization using avian IgY antibodies can protect individuals against a variety of pathogens, including influenza virus. Yet the effect of IgY administration on generation of protective immunity is largely unknown. To address the effect of passive immunization on the host immune response development, adult or aged, male and female C57BL/6NCrl mice received chicken IgY anti-H5N1, normal IgY or PBS intranasally four hours before, and 20 hours after intranasal infection with H1N1 influenza A virus (PR8). The mice receiving cross-reactive IgY anti-H5N1 were protected from disease and developed influenza virus-specific memory T cells similar to control-treated mice. When re-challenged with PR8 35 days post primary infection IgY anti-H5N1-treated mice were fully protected. Moreover, when challenged with heterologous H3N2 influenza A virus (X-31) or with PR8 three months post infection the mice were protected against severe disease and death, albeit a slight transient weight loss was noted. The results show that passive immunization with IgY anti-H5N1 is safe and protects mice against disease induced by influenza virus without inhibiting development of protective immunity after virus exposure. This indicate that passive immunization can be used as prophylactic therapy in combination with immunization to prevent disease.