Sleep-disordered breathing (SDB) is a prevalent disorder characterized by recurrent episodic upper airway obstruction. In a dataset from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we applied principal component analysis (PCA) on seven measures characterizing SDB-associated respiratory events. We estimated the association of the top two SDB PCs with serum levels of 617 metabolites, in both single-metabolite analysis, and a joint, penalized regression analysis using the least absolute shrinkage and selection operator (LASSO). Discovery analysis included n = 3,299 HCHS/SOL individuals; associations were validated in a separate dataset of n = 1,522 HCHS/SOL individuals. Seven metabolite associations with SDB PCs were discovered and replicated. Metabolite risk scores (MRSs) developed based on LASSO association results and representing metabolite signatures associated with the two SDB PCs were associated with 6-year incident hypertension and incident diabetes. MRSs have the potential to serve as biomarkers for SDB, guiding risk stratification and treatment decisions.