Background: Secondary bacterial pneumonia is a common consequence of respiratory viral infections, and is a debilitating and life threatening disease. Studies have revealed many components of the immune response to be dysfunctional, suggesting the presence of multi-factorial immune suppressants such as the PD-1/PD-L pathway. Aim: We aim to demonstrate that PD-1/PD-L signalling is up-regulated during viral infections and their suppressive function predisposes to secondary bacterial pneumonia. Methods: We employed a mouse model of viral predisposition to bacterial pneumonia by infecting mice with pneumonia virus of mice (PVM), and at the time of viral clearance infected them with a mouse-adapted strain of Streptococcus pneumoniae (Spn, D39). PD-1/PD-L expression and immune cell profiles of the lung were analysed by flow cytometry. The role of PD-1 signalling was determined by administration of a PD-1 blocking antibody. Results: Bacterial titres in the lungs of a secondary Spn infection were increased compared to a primary Spn infection alone. Cellular profiles of mice with a prior PVM infection demonstrated reduced activation of APCs, increased Treg numbers, and elevated PD-1 and PD-L1 expressing cells in response to Spn infection. Blocking PD-1 signalling reduced bacterial titres in the lung during secondary Spn infection. Conclusion: A prior PVM infection induces an immunosuppressive environment in the lungs during Spn infection that may hamper the hosts’ ability to clear bacterial infection. We have also demonstrated a pivotal role of PD-1 signalling in the clearance of a secondary bacterial infection. This study also highlights a potential role of PD-1 blocking antibody as a novel therapeutic approach for secondary bacterial pneumonia.