Sleep and wakefulness disorders impact 50 to 70 million Americans and insufficient sleep is epidemic with over 50% of Americans reporting less than 7 hours of sleep per night. Health problems associated with insufficient sleep include inflammation, depression and anxiety, diabetes, stress, drug abuse, poor quality of life, obesity, and fatigue related accidents on the job/while driving. While the contribution of sleep to overall health, well-being, and public safety is recognized, no established clinical biomarkers of sleep deficiency exist. Such biomarkers would have utility as road-side biomarkers of sleepiness (e.g., drowsy driving), monitoring on the job fatigue/fitness for duty (e.g., transportation, military ops health care), monitoring sleep health, as well as for clinical diagnostics and measures of clinical treatment outcomes. Thus, we designed a controlled laboratory insufficient sleep protocol utilizing metabolomics to identify biomarkers of insufficient sleep. Preliminary metabolomics data from our NIH Administrative Supplement awarded to our existing R01 Metabolic and Cognitive Consequences of Sleep Loss set the stage for this proposal and facilitated our proposed discovery and targeted approaches. The current proposal is responsive to key goals of the 2014 Joint Task Force of the Sleep Research Society and American Academy of Sleep Medicine report. We propose to identify changes in metabolites that consistently occur during insufficient sleep. We will also target metabolites identified by our previous research efforts as potential biomarkers. As an exploratory outcome we will examine associated changes in metabolites and cognitive performance during insufficient sleep. These proposed outcomes support the NIH Precision Medicine Initiative and the 2011 NIH Sleep Disorders Research Plan to identify biomarkers of sleep deficiency and enabling sleep and circadian research training in cross-cutting domains to accelerate the pace of discovery and translation.