Streptococcus pneumoniae is the major prevalent pathogen causing community-acquired pneumonia and other invasive diseases like meningitis and sepsis. An event of anti-pneumococcal immune responses is orchestrated by a panel of pattern recognition receptors by innate immune cells, such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs). Dendritic cell (DC)-associated C-type lectin-2 (Dectin-2), a member of the CLR family, is highly expressed in innate immune cells including DCs, macrophages and neutrophils. Dectin-2 recognizes mannose-containing glycoconjugates through its extracellular carbohydrate-recognition domain. Upon ligand-binding, Dectin-2 induces activation of immune responses, including inflammatory cytokine production through the association of ITAM-containing Fc receptor γ chain (FcRγ). We have recently reported that Dectin-2 recognizes mannose-containing capsule components from S. pneumoniae, promotes inflammatory cytokine production and plays a critical role in host defense against S. pneumoniae infection. On the other hand, the importance of Dectin-1, a β-glucan-binding CLR that is expressed in innate immune cells, in control of S. pneumoniae infection remains to be elusive. In this study, we found that Dectin-1 gene expression was increased in the lung of S. pneumoniae-infected mice. Dectin-1-positive cells were infiltrated in the lung from the mice. Dectin-1-Fc, a soluble form of Dectin-1 fused with an IgG Fc domain, bound to several S. pneumoniae strains. The binding was cancelled by β-glucanase treatment. Following stimulation with S. pneumoniae, Dectin-1-overexpressing RAW264.7 cells showed enhanced inflammatory cytokine production compared with parent RAW264.7 cells. Bone marrow-derived dendritic cells (BMDCs) from Dectin-1-deficient mice resulted in impaired inflammatory cytokine production relative to wild type BMDCs. Taken together, these data suggest Dectin-1 plays an important role in innate immune responses to S. pneumoniae infection in the lung.