Purpose High myopia is associated with blinding ocular morbidities. Identifying novel biomarkers may provide clues on pathogenic pathways that are currently unknown. We aimed to identify serum metabolic biomarkers and investigate the metabolic alterations in relation to high myopia. Methods Forty adults with high myopia and 40 with low myopia aged 60 years or older from the Weitang Geriatric Diseases study were included in the case-control study. Refractive error was determined by autorefraction followed by subjective refraction. We performed the metabolomic analysis of serum samples from patients with high myopia and age- and sex- matched controls with low myopia, using a nontargeted gas chromatography coupled to time-of-flight mass spectrometer. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacities of each metabolite marker. Databases including KEGG and MetaboAnalyst were utilized to search for the potential pathways of metabolites. Results Serum metabolomic profiles could well distinguish high myopia from low myopia. Twenty metabolic biomarkers were identified as potential serum biomarkers for high myopia, yielding AUC values of 0.59-0.71. Metabolic pathways in relation to high myopia, mainly characterized by increased energy metabolism, increased oxidative stress, abnormal amino acid metabolism, and altered biotin metabolism, provide a foundation to support myopia progression. Conclusions This study identified valuable metabolic biomarkers and pathways that may facilitate an improved understanding of the disease pathogenesis. The finding holds translational value in the development of new therapeutic measures for high myopia-related complications.