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Objective Controversies exist regarding the relationship between the concentrations of antimicrobial peptides (AMPs) and presence of dental caries in children. Thus, the aim of this study was to examine levels of AMPs in saliva of caries-free (CF), early childhood caries (ECC) and severe early childhood caries (S-ECC) children to determine if the levels of these salivary peptides individually or in combinations were related to caries severity and mutans streptococci levels. Design 36 to 60 month-old children were selected to participate in this study. Children were grouped into CF group (n = 29), ECC group (n = 25) and S-ECC group (n = 29). Saliva was collected from children for microbiological analysis by culture. Salivary concentrations of cathelicidin LL-37, human β-defensin 2 (hBD-2), human β-defensin 3 (hBD-3) and histatin-5 (HTN-5) were determined by ELISA. Results Salivary concentrations of AMPs did not differ among CF, ECC and S-ECC groups. Data showed positive correlations between mutans streptococci levels and salivary hBD-2 or HTN-5. Positive correlations were found between hBD-2, hBD-3, LL-37 and HTN-5. Combinations among AMPs, mainly LL-37, were positively associated with caries levels. Conclusions Salivary concentrations of AMPs individually were not associated with the severity of early childhood caries. The stimulus of caries appears to trigger a biological response, however, with a combination of these peptides. [ABSTRACT FROM AUTHOR]