BACKGROUND Early childhood caries (ECC) is a severe type of dental caries affecting infants and pre-school children. Because of the infectious nature of the disease, the immunologic response by the host plays an essential role in its development. OBJECTIVE This study investigated the association between the presence of salivary sCD14 and ECC. METHODS This study was carried out on 40 healthy children, of whom 20 were caries-free (CF) and 20 had ECC, within the ages of 36 to 71 months. Unstimulated saliva of the children was collected with disposable needle-less syringe from buccal and labial vestibules. Seven children with ECC received complete treatments. Saliva was collected for a second time after 3 months from this group. The sCD14 levels in salivary samples were analyzed by ELISA method. RESULTS Mean concentrations of sCD14 in ECC and CF groups were 57.82 and 31.92 ng/ml respectively (p=0.008). After three months, the mean concentration of sCD14 among the treated children decreased to 11.38 ng/ml, which was significantly lower compared to that of ECC children before intervention (p<0.001), and also CF children (p<0.05). CONCLUSIONS The increased levels of sCD14 can be considered as a marker of inflammation and innate immune response during ECC.