Abstract Although a low incidence cancer, ovarian carcinoma (OvCa) has a high mortality rate due to late detection. To study the humoral immune response to OvCa we transplant ID8 cells (mouse epithelial carcinoma) into the murine peritoneal cavity (PerC). We found that as the OvCa developed PerC B cells, particularly B-1 B cells, were depleted. To assess the systemic impact of this depletion we assessed humoral immunity. We found a reduction in “natural” IgM and IgG3 production and increased IgA and IgG1. Following immunization, there was loss of the TI-2 response (FITC-dextran, FITC-Ficoll); the TI-1 (FITC-LPS) response was intact until very late stage disease. Since B-1 cells also serve a housekeeping role in apoptotic corpse clearance, we used a FACS assay and a cell-based ELISA to monitor antibodies directed at apoptotic ID8 cells. Mice with OvCa had lower titers of sera that bound apoptotic ID8 cells. Collectively these data validate the systemic loss of B-1 B cells in mice with OvCa. These results could serve to inform strategies designed for early detection of OvCa.