Objective: This study employed lipidomics analysis to systematically screen potential biomarkers of childhood obesity comorbid with central precocious puberty (CO-CPP), and explored the feasibility of combining these biomarkers with disease-related clinical indicators to provide new evidence for early identification and warning of CO-CPP. Methods: A total of 20 obese female children aged 6 to 8 years who first visited the Pediatric Endocrinology Clinic of the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University between January 2024 and June 2025 were enrolled. They were divided into the CO-CPP group (n=10) and the comorbidity of childhood obesity comorbid with peripheral precocious puberty (CO-PPP) group (n=10) based on the presence of central precocious puberty (CPP) or peripheral precocious puberty (PPP). General clinical data were compared between the two groups, and serum samples were collected for non-targeted lipidomics analysis. Differential lipids were screened using receiver operating characteristic (ROC) curve analysis, and a combined predictive model was constructed with clinical indicators via binary logistic regression, followed by further combined ROC analysis. Results: Lipidomics analysis identified 42 lipid molecules with significant differences. Among them, the expression of ceramide (Cer) and phosphatidylcholine (PC) were up-regulated, while the expression of phosphatidylethanolamine (PE) was down-regulated. The area under the curve (AUC) of ROC for predicting CO-CPP by Cer, PC, and PE alone was 0.810, 0.798, and 0.834, respectively, all of which showed good discriminative efficacy (all P < 0.05). The AUC of the combined prediction model of Cer and the basal level of luteinizing hormone (LH) was 0.970. Conclusion: In girls with CPP, the expressions of Cer and PC, the key lipids associated with pubertal development, are up-regulated, while the expression of PE is down-regulated. These lipids may serve as potential biological markers for CPP. The discriminative efficacy of Cer combined with basal LH is superior to that of single lipid indicators, showing good potential for clinical application.