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It is unclear whether the metabolic storage lesion is correlated with clinically relevant outcomes and whether strategies aimed at improving the metabolic quality of stored units, such as hypoxic storage, ultimately improve performance in the transfused recipient.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>Twelve healthy donor volunteers were recruited in a two\u2010arm cross\u2010sectional study, in which each subject donated 2 units to be stored under standard (normoxic) or hypoxic conditions (Hemanext technology). End\u2010of\u2010storage measurements of hemolysis and autologous posttransfusion recovery (PTR) were correlated to metabolomics measurements at Days 0, 21, and 42.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Hypoxic red blood cells (RBCs) showed superior PTR and comparable hemolysis to donor\u2010paired standard units. Hypoxic storage improved energy and redox metabolism (glycolysis and 2,3\u2010diphosphoglycerate), improved glutathione and methionine homeostasis, decreased purine oxidation and membrane lipid remodeling (free fatty acid levels, unsaturation and hydroxylation, acyl\u2010carnitines). Intra\u2010 and extracellular metabolites in these pathways (including some dietary purines) showed significant correlations with PTR and hemolysis, though the degree of correlation was influenced by oxygen saturation (SO<jats:sub>2<\/jats:sub>) levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Hypoxic storage improves energy and redox metabolism of stored RBCs, which results in improved posttransfusion recoveries in healthy autologous recipients\u2014a Food and Drug Administration gold standard of stored blood quality. In addition, we identified candidate metabolic predictors of PTR for RBCs stored under standard and hypoxic conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.15730","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T08:27:48Z","timestamp":1582792068000},"page":"786-798","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Hypoxic storage of red blood cells improves metabolism and post\u2010transfusion recovery"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-6490","authenticated-orcid":false,"given":"Angelo","family":"D\u02bcAlessandro","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Denver \u2013 Anschutz Medical Campus  Aurora Colorado"},{"name":"Department of Medicine \u2013 Division of Hematology University of Colorado Denver \u2013 Anschutz Medical Campus  Aurora 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Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1291-7233","authenticated-orcid":false,"given":"Jose A.","family":"Cancelas","sequence":"additional","affiliation":[{"name":"Hoxworth Blood Center University of Cincinnati Academic Health Center  Cincinnati Ohio"},{"name":"Division of Experimental Hematology and Cancer Biology Cincinnati Children\u02bcs Hospital Medical Center  Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14165"},{"key":"e_1_2_8_3_1","first-page":"27","article-title":"Red blood cell storage lesion: causes and potential clinical consequences","volume":"17","author":"Yoshida T","year":"2019","journal-title":"Blood 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