Background: Staphylococcus aureus colonization has been found in 80–100% of lesional skin from patients with atopic eczema dermatitis syndrome (AEDS) and is thought to have a role in the pathogenesis of the disease. Furthermore, up to 65% of S. aureus from lesional skin has been shown to produce toxigenic superantigens. Methods: Using a cohort of 11 children under 2 years of age diagnosed with AEDS, we isolated peripheral blood mononuclear cells, cultured them with staphylococcal enterotoxin B (SEB) and phytohaemagglutinin, and assessed the cytokine response profiles. Plasma was also collected for immunoglobulin E analysis. In addition, skin and nasal swabs were taken and cultured to determine the presence of SEB-producing S. aureus by polymerase chain reaction (PCR) and reverse passive latex agglutination. Results: We found a significant increase in the production of the SEB-induced cytokines interleukin (IL)-5 and IL-13 in the patient group when compared with non-atopic, healthy controls. For IL-13, there was almost no overlap in the levels between the groups. However, there was no correlation between SEB-induced IL-13 and disease severity. This difference was not seen when heat-inactivated S. aureus was used to stimulate the cells. Conclusions: IL-13 is an important factor in AEDS development in early childhood, and prophylactic anti-staphylococcal treatment may provide protection from AEDS in atopic individuals.