Club cell secretory protein is an indirect phospholipase A2 inhibitor with some immunosuppressive and anti-proliferative properties that is expressed in bronchiolar Club cells. In our murine bone marrow transplant (BMT) model of obliterative bronchiolitis (OB) Club cell secretory protein (CCSP) is diminished; however, its role is unknown. To determine the role of CCSP, B6 wild type (WT) or CCSP deficient (CCSP^-/^-) mice were lethally conditioned and given allogeneic bone marrow with a sublethal dose of splenic allogeneic T-cells to induce OB. We found that CCSP ^-/^- mice demonstrated a higher mortality following BMT induced OB compared to WT mice. Mice were analyzed 60 days post-BMT for protein expression, pulmonary lung function, and histology. CCSP levels were reduced in WT mice with BMT induced OB and lower levels correlated to decreased lung compliance. CCSP ^-/^- had a higher degree of injury and fibrosis as measured by hydroxyl proline and increased lung resistance. Replacement with recombinant intravenous CCSP partially reversed the weight loss and increased mortality in the CCSP ^-/^- mice. In conclusion, CCSP is decreased in WT mice that develop OB following a BMT. This decrease in CCSP results in lung injury and fibrosis that was reflected in lung mechanics and decreased survival. Replacing CCSP systemically resulted in improved survival. These findings indicate that CCSP has a regulatory role in OB and may have potential as a preventive therapy.