Objective: Obesity is a significant risk factor for endocrine system abnormalities in children, and obese children exhibit a markedly increased risk of central precocious puberty (CPP). 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 6–8 years who first visited the Pediatric Endocrinology Clinic of the Affiliated Huaian 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 CPP or peripheral precocious puberty (PPP). General characteristics were compared, and non-targeted lipidomics analysis was performed using blood samples. 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 identified 42 lipid types with significant differences. Among them, ceramide (Cer) and phosphatidylcholine (PC) were upregulated, while phosphatidylethanolamine (PE) was downregulated. The Area Under the Curve (AUC) of Cer, PC, and PE alone for predicting CO-CPP was 0.810, 0.798, and 0.834, respectively, demonstrating good discriminative efficacy (p<0.05). The AUC of the combined prediction model of Cer and the basal level of luteinizing hormone (LH) was 0.970. Conclusion: The key lipids associated with CO-CPP in girls, including Cer and PC upregulated and PE downregulated during adolescence, may serve as potential biomarkers for CO-CPP. The discriminant efficiency of Cer and LH was better than that of single index.