Patients treated in the intensive care unit (ICU) for sepsis induced multiple organ failure often suffer from skeletal muscle fatigue after ICU discharge. Since mitochondria are the main determinants of muscle fatigability, their function in muscle of these patients was the theme of this thesis. Decreased muscle mitochondrial activity has been related to mortality in patients suffering from acute sepsis. The present thesis has two major aims. The first is to describe mitochondrial derangements in muscle from septic patients and the second one was to elucidate the underlying mechanisms for these mitochondrial problems. To describe the mitochondrial derangements in muscle from septic patients, muscle biopsies were obtained from respiratory and leg muscle of mechanically ventilated septic patients and healthy control patients. In both muscle tissues a decreased mitochondrial content was found in comparison to controls. In addition, leg muscle had lower concentrations of energy rich phosphates and an increased lactate concentration. The second study relating to this problem was performed in a human model for studying the very early phase of sepsis. In this study leg muscle biopsies were obtained at baseline and 2 and 4 hours after an intravenous endotoxin injection. Mitochondrial enzyme activities increased 2 hours after endotoxin and went back to baseline at 4 hours. The concentration of ATP did not change between baseline and the two consecutive biopsies, however an increase in activity was found between 2 and 4 hours after endotoxin. The second aim was to characterize underlying mechanisms that may cause mitochondrial derangements in septic patients. The effect of inactivity on muscle mitochondria was evaluated in diaphragm muscle from mechanically ventilated piglets. The mitochondrial enzyme activity of complex IV was significantly decreased after 5 days of mechanical ventilation while the other mitochondrial enzymes and content did not change. In the last study mitochondrial protein turnover and biogenesis were ...