Abstract Context: Carotenoids have been implicated in the regulation of adipocyte metabolism. Objective: To compare the effects of mixed-carotenoid supplementation (MCS) versus placebo on adipokines and the accrual of abdominal adiposity in children with obesity. Design and Setting: Randomized (1:1), double-blind, placebo-controlled intervention trial to evaluate the effects of MCS over 6 months in a subspecialty clinic. Participants: Twenty (6 male and 14 female) children with simple obesity [body mass index (BMI) > 90%], a mean age (± standard deviation) of 10.5 ± 0.4 years, and Tanner stage I to V were enrolled; 17 participants completed the trial. Intervention: MCS (which contains β-carotene, α-carotene, lutein, zeaxanthin, lycopene, astaxanthin, and γ-tocopherol) or placebo was administered daily. Main Outcome Measures: Primary outcomes were change in β-carotene, abdominal fat accrual (according to magnetic resonance imaging), and BMI z-score; secondary outcomes were adipokines and markers of insulin resistance. Results: Cross-sectional analysis of β-carotene showed inverse correlation with BMI z-score, waist-to-height ratio, visceral adipose tissue, and subcutaneous adipose tissue (SAT) at baseline. MCS increased β-carotene, total adiponectin, and high-molecular-weight adiponectin compared with placebo. MCS led to a greater reduction in BMI z-score, waist-to-height ratio, and SAT compared with placebo. The percentage change in β-carotene directly correlated with the percentage change in SAT. Conclusions: The decrease in BMI z-score, waist-to-height ratio, and SAT and the concomitant increase in the concentration of β-carotene and high-molecular-weight adiponectin by MCS suggest the putative beneficial role of MCS in children with obesity.