Introduction: Systemic inflammation is a well-known risk factor for respiratory muscle weakness. Studies using animal models of inflammation have shown that endotoxin administration induces diaphragm dysfunction. However, the effects of in vivo endotoxin administration on diaphragm function in humans have not been studied. Our aim was to evaluate diaphragm function in a model of systemic inflammation in healthy subjects. Methods: Two groups of 12 male volunteers received an intravenous bolus of 2 ng/kg of Escherichia coli lipopolysaccharide (LPS) and were monitored until 8 h after LPS administration. In the first group, the twitch transdiaphragmatic pressure (Pditw) and compound muscle action potential of the diaphragm (CMAPdi) were measured. In addition, plasma levels of cytokines, heart rate, and arterial blood pressure were measured. In the second group, catecholamines as well as respiratory rate and blood gas values were measured. Diaphragm ultrasonography was performed in four subjects with severe shivering. Results: Lipopolysaccharide administration resulted in flulike symptoms, hemodynamic alterations, and increased plasma levels of cytokines. The Pditw increased after LPS administration from 31.2±2.0cmH2O (baseline) to 38.8±2.0cmH2O (t=1 h) and 35.4±2.0cmH2O (t=1.5 h). There was no correlation between cytokine plasma levels and the Pditw. We found a trend toward a gradual decrease in the CMAPdi from 0.78±0.07mV (baseline) to 0.58±0.05mV (t=2 h). Respiratory rate increased after LPS administration from 16.8±0.5 breaths/min (baseline) to 20.3±0.6 breaths/min (t=4 h), with a resulting decrease in PaCO2 of 0.5±0.1 kPa. Plasma levels of epinephrine peaked at t=1.5 h, with an increase of 1.3±0.3 nmol/L from baseline. Rapid diaphragm contractions consistent with shivering were observed. Conclusions: This study shows that, in contrast to diaphragm dysfunction observed in animal models of inflammation, in vivo diaphragm contractility is augmented in the early phase after low-dose endotoxin administration in humans.