AbstractBackgroundThe relevance of mitochondrial dysfunction as to pathogenesis of multiple organ dysfunction and failure in sepsis is controversial. This focused review evaluates the evidence for impaired mitochondrial function in sepsis.DesignReview of original studies in experimental sepsis animal models and clinical studies on mitochondrial function in sepsis. In vitro studies solely on cells and tissues were excluded. PubMed was searched for articles published between 1964 and July 2012.ResultsData from animal experiments (rodents and pigs) and from clinical studies of septic critically ill patients and human volunteers were included. A clear pattern of sepsis‐related changes in mitochondrial function is missing in all species. The wide range of sepsis models, length of experiments, presence or absence of fluid resuscitation and methods to measure mitochondrial function may contribute to the contradictory findings. A consistent finding was the high variability of mitochondrial function also in control conditions and between organs.ConclusionMitochondrial function in sepsis is highly variable, organ specific and changes over the course of sepsis. Patients who will die from sepsis may be more affected than survivors. Nevertheless, the current data from mostly young and otherwise healthy animals does not support the view that mitochondrial dysfunction is the general denominator for multiple organ failure in severe sepsis and septic shock. Whether this is true if underlying comorbidities are present, especially in older patients, should be addressed in further studies.