Marginal zone (MZ) B cells bridge innate and adaptive immunity by sensing bloodborne antigens and producing rapid antibody and cytokine responses. CD55 is a membrane-bound complement regulator that interferes with complement activation, an important component of innate immunity. CD55 also regulates adaptive immunity-CD55 downregulation is critical for germinal center reactions. MZ B cells also express low CD55, but its role in MZ B cell function is unknown. Using germline knockout mice, we found that similar numbers of MZ B cells are initially established in 3-week-old CD55-deficient mice compared to wild-type (WT) mice. However, MZ B cells fail to accumulate as mice age and undergo increased apoptosis. Following ex vivo stimulation of MZ B cells through Toll-like receptor 9, we observed a proinflammatory phenotype with increased IL-6 expression. These findings demonstrate a critical role for CD55 in supporting MZ B cell survival while also regulating cellular function.