Abstract Objective Oxidative stress is suspected in the development of obesity. We sought to evaluate the relationship between oxidative stress and obesity/adiposity in early childhood, and explore potential sex dimorphic associations. Design Nested case–control study. Methods In a study of 120 pairs of children with overweight/obesity vs. optimal weight in the Shanghai Birth Cohort, we assessed oxidative stress (urinary biomarker 8-isoprostane) in relation to obesity/overweight and adiposity indicators [body mass index (BMI, z-score), body fat mass (BFM), and percent body fat (PBF)] in early childhood (age 4 years). Results Urinary 8-isoprostane concentrations were higher in overweight/obese vs. optimal weight children in males (2.23 ± 1.68 vs. 1.60 ± 1.01 ng/mg creatinine, P = .001), but similar in females (1.74 ± 1.81 vs. 1.81 ± 0.94, P = .26). Positive correlations were observed in 8-isoprostane with BMI z-score (r = 0.34, P < .001), BFM (r = 0.28, P < .001), and PBF (r = 0.26, P = .002) in males, while no correlation was observed in females. Adjusting for maternal and child factors, one log unit increment in urinary 8-isoprostane concentration was associated with a 0.72 (95% CI .31-1.13) increase in BMI z-score, 1.02 (0.12-1.19) kg increase in BFM, and 3.09% (0.01%-6.17%) increase in PBF in males, respectively. Conclusions Oxidative stress levels were elevated in overweight/obesity children, and positively correlated with adiposity in males only, suggesting sex-dimorphic associations between oxidative stress and adiposity/obesity in early childhood.