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Objectives: There is increasing interest in hydrogen sulfide as a marker of pathologic conditions or predictors of outcome. We speculate that as hydrogen sulfide is a diffusible molecule, if there is an increase in plasma hydrogen sulfide in sepsis, it may accumulate in the alveolar space and be detected in exhaled gas. We wished to determine whether we could detect hydrogen sulfide in exhaled gases of ventilated children and neonates and if the levels changed in sepsis., Design: Prospective, observational study., Setting: The study was conducted across three intensive care units, pediatric, neonatal and cardiac in a large tertiary children's hospital., Patients: We studied ventilated children and neonates with sepsis, defined by having two or more systemic inflammatory response syndrome criteria and one organ failure or suspected infection. A control group of ventilated non-septic patients was also included., Intervention: A portable gas chromatograph (OralChroma; Envin Scientific, Chester, United Kingdom) was used to measure H2S in parts per billion., Measurements and Main Results: A 1-2 mL sample of expired gas was taken from the endotracheal tube and analyzed. A repeat sample was taken after 30 minutes and a further single daily sample up to a maximum of 5 days or until the patient was extubated. WBC and C-reactive protein were measured around the time of gas sampling. Each group contained 20 subjects. Levels of H2S were significantly higher in septic patients (Mann Whitney U-test; p < 0.0001) and trended to control levels over five days. C- reactive protein levels were also significantly raised (p < 0.001) and mirrored the decrease in H2S levels., Conclusion: Hydrogen sulfide can be detected in expired pulmonary gases in very low concentrations of parts per billion. Significantly higher levels are seen in septic patients compared with controls. The pattern of response was similar to that of C-reactive protein.