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Labor dystocia, a leading indication for cesarean delivery, disproportionately affects African American women, yet its metabolic underpinnings remain poorly understood. The objective of this study was to characterize prenatal serum lipidomic signatures associated with term labor dystocia in African American women. Untargeted lipidomics was performed on serum collected at early (8–14 weeks) and late-pregnancy (24–30 weeks) from 43 labor dystocia cases matched to 43 rapid labor controls on parity, BMI, age and mode of labor onset. Analyses included PLS-DA, weighted lipid co-expression network analysis, community structure analysis, and longitudinal difference-of-difference modeling. Labor dystocia was characterized by reduced circulating LPC, ceramide, and sphingomyelin in early pregnancy alongside elevated polyunsaturated PE and PI species. Late pregnancy was marked by progressive accumulation of saturated and oleic acid-containing triglycerides. Network analysis revealed reorganization of inter-module lipid relationships with loss of negative regulatory correlations in dystocia. Integrating longitudinal lipid trajectories yielded superior predictive performance (AUC 0.979) compared to single time-point models. Labor dystocia is preceded in pregnancy by a disrupted circulating lipid signature, providing preliminary leads for future research to support early risk stratification and understanding of the mechanisms underlying prolonged labor.