The objective was to investigate whether there is any correlation between signs of central and peripheral immune stimulation in victims of sudden infant death syndrome (SIDS), the former expressed by IL-6 in cerebrospinal fluid (CSF), the latter by IgA, IgG, and IgM immunocytes, T lymphocytes, and HLA-DR expression in laryngeal mucosa. Seventeen SIDS cases with low CSF IL-6 levels (≤5 pg/mL) and 20 cases with high CSF IL-6 levels (≥30 pg/mL) were subjected to immunohistochemical quantitation of IgA, IgG, and IgM immunocytes; semiquantitative scoring of T lymphocytes in the mucosa of epiglottis and larynx, and semiquantitative evaluation of HLA-DR expression. SIDS cases with IL-6 levels ≥30 pg/mL had a significantly higher number of IgA immunocytes in laryngeal mucosa (p = 0.007) and in epiglottis (p = 0.03) than cases with IL-6 levels ≤5 pg/mL. Furthermore, laryngeal HLA-DR expression was significantly more extensive in SIDS cases with IL-6 levels ≥30 pg/mL than in those with levels ≤5 pg/mL (p = 0.05). No differences were found for IgG and IgM immunocytes or for T cells. In addition, babies found prone more often had symptoms of slight infection before death and had a higher number of IgA immunocytes in the larynx (p = 0.02) than babies sleeping on their side or back. Because IL-6 levels ≥30 pg/mL correspond to the levels found in infants who die from infectious diseases such as meningitis/septicemia and pneumonia, the findings favor the hypothesis that many SIDS cases may be caused by an "overreaction" of the immune system to an otherwise harmless infection.