Background: Persistent carriers have an increased risk of Staphylococcus aureus infections, but a lower risk of bacteremia-related death than non-carriers. Here, a role for antistaphylococcal antibodies was studied. Methods: Sera of fifteen persistent and nineteen non-carriers were analyzed for IgG, IgA and IgM binding to nineteen S. aureus antigens, using Luminex technology. Also, sera obtained after six months and nasal secretions were analyzed. Results: Median IgG serum levels were significantly higher in persistent than non-carriers for toxic shock syndrome toxin-1 (TSST-1; Median Fluorescence Intensity (MFI) 11554 vs. 4291, p<0.001) and staphylococcal enterotoxin A (SEA; 742 vs. 218, p<0.05); median IgA levels were higher for TSST-1 (p<0.01), SEA, Clumping factor A and B (ClfA and ClfB; p<0.05). The neutralizing capacity of anti-TSST-1 antibodies correlated to the MFI value (R2=0.93) and was higher in persistent carriers (median 90.6% vs. 70.6%, p<0.05). Antibody levels were stable over time and correlated with levels in nasal secretions (IgG: R2=0.87; IgA: R2=0.77). Conclusions: Median antibody levels to TSST-1, SEA, ClfA and ClfB are higher in persistent than non-carriers and antibodies to TSST-1 have neutralizing capacity. These antibodies might be associated with the difference in risk and outcome of S. aureus infections in nasal carriers versus non-carriers.