Systemic enterococcal infections often lead to life-threatening disease. By analyzing the immune response of two patients with systemic enterococcal infections against enterococcal polysaccharide antigens, we found that both patients had antibodies against all four of the capsular serotypes identified to date. Antibody concentrations against the causative capsular serotype were in the same range as antibodies against the other three capsular protoserotypes. Interestingly, we noted a difference between the two patients with respect to opsonic activity in the killing assay: one patient showed better killing of all four capsular prototypes than the other. However, killing against the infecting serotype was not increased in comparison to killing of the other serotypes in the two patients. This finding supports previously published data that most healthy humans possess preexisting, naturally acquired, anti-enterococcal antibodies. We conclude, therefore, that systemic infection with enterococci does not lead to higher antibody concentrations or better opsonic killing against the causative capsular serotype.