The innate immune response facilitates the quality of the adaptive immune response and is critical to an individual's susceptibility to infection and disease. Mannose-binding lectin (MBL) is a plasma protein with anti-microbial properties that binds a wide range of pathogens to flag them for immune destruction independent of antibodies. In this study, serum MBL levels were measured in 81 children <5 years old experiencing acute respiratory syncytial virus infection and in 40 control children to determine the association with disease severity. Almost 70% of all RSV-infected children had low to intermediate MBL levels (<500 ng/ml) compared to controls, and most of the <6 months old RSV interned patients had low to intermediate levels. No differences were detected in MBL levels between case and control children <1 month old. Analysis of the T-cell compartment in peripheral blood mononuclear cells (PBMC) from acute RSV-infected and control children showed that the percent CD4+ T cells was statistically lower in RSV-infected children > or =6 months old compared to controls, while the percent CD8+ T cells in RSV-infected and control PBMC was generally similar. These results suggest that low serum MBL levels may be a marker of RSV disease severity in children and that MBL may be important in limiting RSV disease pathogenesis.