Introduction The therapeutic value of intravenous immunoglobulin (IVIG) as an adjuvant therapy in sepsis remains debatable. We hypothesized that intravenous administration of BT086, a predominantly IgM IVIG solution, would improve host defense in an established rabbit model of endotoxemia and systemic sepsis. Methods New Zealand white rabbits were randomized into the following four groups: (1) the negative control group without lipopolysaccharide (LPS, control), (2) the positive control group with LPS infusion (LPS group), (3) the albumin-treated LPS group (ALB+LPS group), and (4) the BT086-treated LPS group (BT086 + LPS group). A standardized amount of E. coli was intravenously injected into all of the animals. The vital parameters, the concentration of E. coli in the blood and other organs, the residual granulocyte phagocytosis activity, and the levels of the inflammatory mediators were measured. Histological changes in the lung and liver tissue were examined following autopsy. Results The elimination of E. coli from the bloodstream was expedited in the BT086-treated group compared with the LPS- and albumin-treated groups. The BT086 + LPS group exhibited higher phagocytic activity of polymorphonuclear neutrophils (PMNs) than the control and ALB+LPS groups. The liver energy stores were higher in the BT086 + LPS group than in the other groups. Conclusion Our data suggest that the IgM-enriched IVIG has the potential to improve host defense in a rabbit model of endotoxemia. Studies using different animal models and dosages are necessary to further explore the potential benefits of IgM-enriched IVIG solutions.