Aging alters immunoglobulin production, affecting the humoral immune response. Toll-like receptor 2 (TLR2) recognizesStaphylococcus aureus(S. aureus) which causes bacteremia with high mortality in the elderly. To understand how TLR2 and aging affect the humoral immune response in bacteremia, four groups of mice (wild type-young, wild type-old, TLR2−/−-young, and TLR2−/−-old) were used to analyze immunoglobulin levels in healthy conditions as well as 10 days after intravenous injection withS. aureus. We found that aging increased the levels of both IgM and IgG. Increased IgG in aged mice was controlled by TLR2. In bacteremia infection, aged mice failed to mount proper IgM response in both wild-type (WT) and TLR2−/−mice, whereas IgG response was impaired in both aged and TLR2−/−mice. Aged mice displayed reduced IgG1 and IgG2a response irrespective of TLR2 expression. However, impaired IgG2b response was only found in aged WT mice and not in TLR2−/−mice. Both aging and TLR2−/−increased the levels of anti-staphylococcal IgM in bacteremia. Aging increased sialylated IgG in WT mice but not in TLR2−/−mice. IgG sialylation was not affected by the infection in neither of the mice. In summary, aging increases all immunoglobulins except IgG1. However, aged mice fail to mount a proper antibody response toS. aureusbacteremia. TLR2 plays the regulatory role in IgG but not IgM response to infection.