Background <p>Early childhood caries (ECC) is one of the most prevalent chronic diseases in children and is associated with inflammatory and oxidative processes. This study aimed to evaluate salivary oxidative stress biomarkers and oxidative DNA damage in children with ECC and severe ECC (S-ECC).</p> Methods <p>This cross-sectional study included 90 children aged 2–6 years (control, <i>n</i> = 29; ECC, <i>n</i> = 30; S-ECC, <i>n</i> = 31).Salivary total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), arylesterase (ARES), asprosin, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were analyzed. Correlation and multivariate regression analyses were performed to evaluate the associations between biomarkers and caries severity.</p> Results <p>TAS levels differed significantly among the groups (<i>p</i> = 0.014) and were significantly lower in the ECC group than in the control and S-ECC groups. In contrast, 8-OHdG levels were significantly higher in the S-ECC group than in the control group (<i>p</i> = 0.013). No significant differences were observed among the groups regarding asprosin (<i>p</i> = 0.901), TOS (<i>p</i> = 0.865), OSI (<i>p</i> = 0.422), or ARES levels (<i>p</i> = 0.471). A weak negative correlation was observed between age and 8-OHdG levels (<i>r</i> = − 0.253, <i>p</i> = 0.016). Multivariable regression analysis demonstrated that ECC was independently associated with lower TAS levels (<i>p</i> = 0.011), whereas S-ECC was independently associated with higher 8-OHdG levels (<i>p</i> = 0.003).</p> Conclusions <p>ECC is associated with alterations in salivary oxidative stress biomarkers, characterized by reduced antioxidant capacity and increased oxidative DNA damage in more severe forms of the disease. These findings suggest that oxidative stress may contribute to ECC progression and support the potential role of salivary biomarkers in evaluating disease severity and oxidative tissue damage during early childhood.</p>