Infections associated with Down Syndrome (DS) are prevalent in the mucosal-gastrointestinal and respiratory systems, for reasons that are uncertain. The purpose of the present study was to assess the levels of parotid salivary immunoglobulins (Ig) in a group of DS individuals as a possible factor in the susceptibility of mucosal surfaces to infections. Twenty-nine DS and 10 age- and sex-matched healthy individuals were included. Salivary flow rate and IgA, IgG, and IgM concentrations were recorded. The secretion rates of IgA and IgG were diminished by 83% (p < 0.001) and 75% (p = 0.05), respectively, whereas the secretion rate of IgM was not statistically significantly lower. Analysis of the data suggests that DS individuals are immunodeficient in the humoral mucosal immune response. This may explain, in part, the high incidence of recurrent infections in target organs of the secretory immune system in DS subjects.