Abstract: Vascular tone alteration in sepsis is attributed to nitric oxide (NO) overproduction. Endogenously released carbon monoxide (CO) has been recently proposed to induce excessive vascular relaxation. We aimed 1) to study plasma levels of NO, CO and blood methemoglobin (metHb) in sepsis and sepsis induced organ failure in critically ill children. 2) to determine their relationship to disease severity and outcome. Plasma levels of NO, CO and blood metHb were assessed in 30 critically ill and 14 healthy children. Patients were classified into septic and sepsis induced multi-organ failure (MOF) groups. All patients showed significantly higher plasma levels of NO, CO and blood metHb when compared to controls (p< 0.001). Sepsis induced MOF group attained higher plasma levels of NO and CO and blood metHb compared to septic group (p< 0.001). Children requiring vasopressors showed increased plasma levels of NO, CO and blood metHb compared to those not requiring it (p< 0.001, < 0.05, < 0.001, respectively). Significant positive correlations existed between PRISM score with plasma NO, CO and blood metHb. Non-survivors exhibited higher plasma levels of NO, blood metHb (p< 0.001) and CO (p< 0.05) compared to survivors. In conclusion, plasma NO, CO levels and blood metHb were elevated in sepsis and sepsis induced MOF. They can be used as prognostic markers for disease severity and outcome. We recommend adding plasma CO and blood metHb to standard laboratory tests in Pediatric Intensive Care Units (PICU).