Lipids are molecules involved in metabolism and inflammation . This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children . Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28 . Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive . Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores . Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p -value = 0.004), total phosphatidylserine (PS) (p -value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p -value = 0.03) after adjusting for sex and age . Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake . Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.