Excessive reactive oxygen species (ROS) are detrimental to immune cellular functions that control pathogenic microbes; however, the mechanisms are poorly understood. Our aim was to determine the immunological consequences of increased ROS levels during acute bacterial infection. We used a model of S (Spn) lung infection and superoxide dismutase 3-deficient (SOD3) mice, as SOD3 is a major antioxidant enzyme that catalyses the dismutation of superoxide radicals. First, we observed that , macrophages from SOD3 mice generated excessive phagosomal ROS during acute bacterial infection. , there was a significant reduction in infiltrating neutrophils in the bronchoalveolar lavage fluid and reduced peribronchial and alveoli inflammation in SOD3 mice 2 days after Spn infection. Annexin V/propidium iodide staining revealed enhanced apoptosis in neutrophils from Spn-infected SOD3 mice. In addition, SOD3 mice showed an altered macrophage phenotypic profile, with markedly diminished recruitment of monocytes (CD11c, CD11b) in the airways. Further investigation revealed significantly lower levels of the monocyte chemokine CCL-2, and cytokines IL-23, IL-1β, and IL-17A in Spn-infected SOD3 mice. There were also significantly fewer IL-17A-expressing gamma-delta T cells (γδ T cells) in the lungs of Spn-infected SOD3 mice. Our data demonstrate that SOD3 deficiency leads to an accumulation of phagosomal ROS levels that initiate early neutrophil apoptosis during pneumococcal infection. Consequent to these events, there was a failure to initiate innate γδ T cell responses. These studies offer new cellular and mechanistic insights into how excessive ROS can regulate innate immune responses to bacterial infection.