Sepsis is one of the leading causes of death in hospitals worldwide. Even with optimal therapy, severe sepsis results in 50% mortality, indicating variability in the response of individuals towards treatment. We hypothesize that the presence of pre-existing antibodies present in the blood before the onset of sepsis induced by cecal ligation and puncture (CLP) in mice, accounts for the differences in their survival. A Plasma Enhanced Killing (PEK) assay was performed to calculate the PEK capacity of plasma i.e. the ability of plasma to augment PMN killing of bacteria. PEK was calculated as PEK= (1/log (N)) × 100; where N= number of surviving bacteria; a higher PEK indicated better bacterial killing. A range of PEK in plasma collected from mice prior to CLP was observed, documenting individual differences in bacterial killing capacity. Mortality was predicted based on plasma IL-6 levels at 24 hr post CLP. Mice predicted to die (Die-P) had a lower PEK (<14) and higher peritoneal bacterial counts 24 hr post sepsis compared to those predicted to live (Live-P) with a PEK>16. Mice with PEK<14 were 3.1 times more likely to die compared to the PEK>16 group. To understand the mechanism of defense conferred by the pre-existing antibodies, binding of IgM or IgG to enteric bacteria was documented by flow cytometry. To determine the relative contribution of IgM or IgG, the immunoglobulins were specifically immuno-depleted from the naïve plasma samples and the PEK of the depleted plasma measured. Compared to naïve plasma, depletion of IgM had no effect on the PEK. However, depletion of IgG increased PEK suggesting that an inhibitory IgG binds to antigenic sites on bacteria preventing optimal opsonization of the bacteria. These data demonstrate that prior to CLP; circulating inhibitory IgG antibodies exist that prevent bacterial killing by PMNs in a CLP model of sepsis.