Sepsis produces a characteristic hypermetabolic and hyperdynamic circulatory state. If this response is not reversed, multiple organ failure follows with a high mortality rate. The cellular dysfunction that results in overt organ failure is not clear. Changes in oxygen delivery and consumption in septic patients have raised questions concerning the adequacy of cellular energy stores to maintain cellular function and integrity. Animal septic models have, however, allowed direct determinations of adenosine triphosphate (ATP) and mitochondrial function and correlation with other measurements of cell function. In fact, studies indicate that cellular energy stores and mitochondrial function are well-maintained at a time when cellular abnormality can be demonstrated. In early sepsis, is, 10 hours following cecal ligation and puncture, abnormalities in cell membrane function and membrane potential are present, while ATP levels are maintained. In addition, although there is an absolute increase in the rate of gluconeogenesis, the response to substrate and hormonal stimulation in isolated perfused liver from rats in early sepsis is altered. In late sepsis, is, 16 hours after cecal ligation and puncture, ATP levels decrease and lactate increases. These findings are consistent with tissue hypoxia resulting from hypoperfusion in late sepsis. Thus, it appears that cellular functions are adversely affected in early sepsis, suggesting that the persistence of deleterious effects of sepsis, if not reversed, may lead to organ failure. Certainly, when hypoperfusion occurs in this setting, cellular energy stores appear to decrease, increasing the risk of organ failure and death. © 1990.