Objective: To estimate the association between Social Determinants of Health (structural and intermediate) and caries indicators in Chile's Metropolitan Region preschool children. Methods: A multilevel cross-sectional study of Social Determinants of Health (SDH) and caries in children aged 1 to 6 years in Chile's Metropolitan Region was conducted in 2014–2015, with three levels: district, school and child. Caries were assessed by the dmft-index and the prevalence of untreated caries. The structural determinants analyzed were Community Human Development Index (CHDI), urban/rural location, school type, caregiver's education and family income. Poisson multilevel regression models were fit. Results: The sample size was 2,275 children from 40 schools in 13 districts. While the highest CHDI district had an untreated caries prevalence of 17.1% (12.3–22.7%), in the most disadvantaged district it was 53.9% (95% CI 46.0–61.6%). As family income increased, the probability of untreated caries prevalence decreased (PR = 0.9 95% CI 0.8–1.0). Rural districts had an average dmft-index of 7.3 (95% CI 7.2–7.4), while in urban districts, it was 4.4 (95% CI 4.3–4.5). Higher probabilities of untreated caries prevalence (PR = 3.0 95% CI 2.3–3.9) were observed in rural children. Greater probabilities of untreated caries prevalence (PR = 1.3 95% CI 1.1–1.6) and prevalence of caries experience (PR = 1.3 95% CI 1.1–1.5) were observed in children whose caregivers had a secondary educational level. Conclusions: A strong association was observed between the social determinants of health, specifically the structural ones, and the caries indicators studied in children of the Metropolitan Region of Chile. There were notable differences in caries between districts according to social advantage. Rurality and caregiver's education were the most consistent predictors.