Secondary bacterial infection after respiratory syncytial virus (RSV) infection may lead to severe respiratory diseases, such as pneumonia and hospitalization especially in infants and elderly people. However, the immunological mechanism by which RSV infection causes secondary bacterial pneumonia has not been elucidated. We have recently found that growth arrest-specific 6 (Gas6) and its receptor, Axl signal is important for immune regulation in some infectious diseases, which led us to investigate whether and how the signal is involved in the regulation of immune responses during RSV infection followed by bacterial infection. To elucidate the role of Gas6/Axl signal in this study, we initially examined the immune response in wild type (WT) mice and Gas6 deficient (KO) mice infected with Streptococcus pneumoniae (S. pneumoniae) at day-8 after RSV infection. A survival rate, body weight, and bacterial clearance of co-infected WT mice were significantly decreased after day-3 post S. pneumoniae infection compared with those of Gas6 KO mice. As for inflammation, the number of infiltrated cells and the production of IFN-γ, NO, and TNF-α in Gas6 KO mice were more significantly increased than in WT mice at day-1 post S. pneumoniae infection. These responses were resolved in Gas6 KO mice at day-6 post S. pneumoniae infection, whereas these were dramatically increased in WT mice. Targeting Axl by monoclonal antibody and inhibitor also showed similar results as in Gas6 KO mice, suggesting that Gas6/Axl signal suppresses initial immune responses to bacterial infection. Finally, RSV infection that induces Gas6/Axl signal significantly suppressed IFN-γ production by NK cells via suppressing IL-18 production by macrophages at day-1 post S. pneumoniae infection. Taken together, these results demonstrate that RSV-induced Gas6/Axl signal suppresses the initial inflammatory response associated with S. pneumoniae infection, which ultimately leads to more severe infection.