Background: Bacterial lysates, as immunomodulators, may play a role in regulating the host immune response. Objectives: This study aimed to investigate the effects of bacterial lysates OM85-BV in treating pulmonary infections caused by Streptococcus pneumoniae in children. Methods: A total of 120 children with S. pneumoniae pulmonary infection were divided into two groups: The control group and the OM85-BV group, with a 1: 1 ratio. The control group received intravenous mezlocillin at 100 mL/kg/d, while the OM85-BV group, in addition to mezlocillin, received OM85-BV orally at 3.5 mg per dose. The improvement of clinical symptoms and pulmonary function indexes—including respiratory rate, tidal volume, volume to peak expiratory flow as a proportion of exhaled volume, and time to peak tidal expiratory flow as a proportion of expiratory time—were compared. Additionally, levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R), T lymphocyte subsets, and immunoglobulins in serum were analyzed. Results: Compared to the control group, the OM85-BV group showed a significant decrease in respiratory rate and an increase in tidal volume, volume to peak expiratory flow, and time to peak tidal expiratory flow (P < 0.05 for all). The OM85-BV group also had significantly lower levels of serum inflammatory factors such as CRP, TNF-α, IL-6, and sIL-2R. In terms of immune function, the OM85-BV group showed increased levels of T lymphocyte subsets CD3+, CD4+, and CD4+/CD8+ ratios, with a decrease in CD8+, as well as elevated serum IgA and IgG levels. The total effective rate of treatment in the OM85-BV group was significantly higher than in the control group (P < 0.05). Conclusions: The addition of OM85-BV to the treatment of S. pneumoniae pulmonary infection in children significantly improves clinical symptoms, lung function, and immune function, while reducing the inflammatory response. OM85-BV appears to inhibit the activation of the toll-like receptors (TLRs) and nuclear factor kappa-B (NF-κB) pathway.