The aim of this study was to compare total IgA in the whole saliva of children with Down syndrome with levels in sibling and parent groups. IgA measurements were presented as the concentration in saliva (μg/ml) and also adjusted for salivary flow rate (SFR; μg/min). Twenty children with Down syndrome, ten siblings and twenty parents were recruited. Stimulated whole saliva was collected from the participants and SFR calculated. The measurement of salivary IgA (sIgA) was carried out using an indirect competitive Enzyme-Linked Immunosorbent Assay. The difference in the mean SFR between children with Down syndrome, parents and siblings were not statistically significant. The mean salivary concentration of IgA was higher in children with Down syndrome (95.1 μg/ml) compared with siblings (48.3 μg/ml; p = 0.004). When adjusted for SFR children with Down syndrome had mean sIgA levels of 98.8 μg/min and the siblings 48.6 μg/min (p = 0.008). The children with Down syndrome had sIgA levels similar to those of the parents (92.5 μg/ml; 93.2 μg/min). There was a positive correlation between age and sIgA concentration in the siblings (p = 0.008) but not for children with Down syndrome (p = 0.363). This suggests that under similar environmental influences, the levels of sIgA in children with Down syndrome are higher than in the siblings, from a very young age.