Objective <p>Our study aimed to investigate the link between serum carotenoids and obesity in a large, representative children and adolescents.</p> Methods <p>We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey 2017–2018. The impact of individual exposure to six serum carotenoids (α-carotene, β-carotene, α-cryptoxanthin, β-cryptoxanthin, combined lutein/zeaxanthin, and total lycopene) on adiposity measures, including BMI and obesity, was assessed through survey-weighted logistic and linear regression models. Weighted quantile sum (WQS) regression was adopted to estimate the effect of exposure to a combination of six serum carotenoids on adiposity measures.</p> Results <p>Our study included 1,329 child and adolescent participants (mean age 12.84 years, 50.11% male). The overall mean BMI was 22.03&#xa0;kg/m² (SE = 0.16), with 324 participants (24.39%) classified as obese. After adjusting for potential confounders, higher levels of all serum carotenoids (α-carotene, β-carotene, α-cryptoxanthin, β-cryptoxanthin, and combined lutein/zeaxanthin) except lycopene were associated with lower BMI and prevalence of obesity in children and adolescents. In addition, there was a negative correlation between the combination of all six carotenoids and BMI (β=-1.56, 95% CI: -1.95, -1.16, <i>P</i> &lt; 0.01) and obesity (OR = 0.48, 95% CI: 0.39, 0.60, <i>P</i> &lt; 0.01), with β-carotene having the greatest weighting in body mass index and prevalence of obesity, 0.708 and 0.709.</p> Conclusions <p>Our study provides evidence that serum carotenoids, in particular β-carotene, may be associated with a lower prevalence of obesity in children and adolescents.</p>