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BACKGROUND: Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large-scale single- and pathway-level metabolomics analyses.METHODS: Metabolomics data were available for 877 metabolites in 6071 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). EDS was assessed using the Epworth Sleepiness Scale (ESS) questionnaire. We performed linear regression for each metabolite on the continuous ESS score, adjusting for demographic, lifestyle, and physiological confounders, and in sex specific groups. Subsequently, gaussian graphical modelling was performed coupled with pathway and enrichment analyses to generate a holistic interactive network of the metabolomic profile of EDS associations.FINDINGS: We identified seven metabolites belonging to steroids, sphingomyelin, and long-chain fatty acids sub-pathways in the primary model associated with EDS, and an additional three metabolites in the male-specific analysis.INTERPRETATION: Our findings indicate that an EDS metabolomic profile is characterised by endogenous and dietary metabolites within the steroid hormone biosynthesis pathway, with some pathways that differ by sex. These pathways may be useful for understanding the causes or consequences of EDS and related sleep disorders.FUNDING: Details regarding funding supporting this work and all studies involved are provided in the acknowledgements section.