Metabolomics of the REDS RBC Omics recalled donor population. An initial screening for hemolytic propensity of RBCs at the end of storage (day 42) was performed on 13 403 index donors who were enrolled at 4 different American blood centers. Donors with the highest and lowest hemolytic parameters (5th and 95th percentile) were invited to donate a second unit of blood, and metabolomics analyses were performed on RBC units from 643 recalled donors on storage days 10, 23, and 42 (A). Unsupervised (principal component analysis [PCA]) (B), partially supervised (partial least square–discriminant analysis [PLS-DA]), (C) and hierarchical clustering analysis. Top 50 metabolites by time series analysis of variance in (D) showed a significant impact of storage duration and storage additive solutions on the metabolic variance across the 1929 samples tested in this study. Previously reported metabolic markers of the storage lesion were confirmed among the top variables increasing and decreasing over storage (E). uMAP confirmed a strong impact of storage duration and additives, though an additional subgroup was identified; 3-dimensional [3D] and 2D views (F-G). Top discriminants across these groups were AS components citrate (highest in AS-3) and mannitol (highest in AS-1 in this study) (H). ATP, adenosine triphosphate.