BACKGROUND: Cellular Injury Score (CIS) is an index of cellular injury, being calculated from three parameters of intracellular metabolism: arterial ketone body ratio, osmolality gap, and blood lactate. METHODS: The usefulness of CIS as a severity scoring system for patients with multiple organ failure was prospectively evaluated in 157 consecutive patients with MOF (58 survivors, 99 nonsurvivors). RESULTS: CISs in nonsurvivors were significantly higher compared with those in survivors throughout the clinical courses. CIS was significantly correlated with the number of failing organs and mortality rate. The optimal cutoff point of CIS from receiver operating characteristics curve analysis was 4 for the maximal value during the clinical course. The changes in CIS well reflected the severity of injury in survivors and nonsurvivors who died within 2 weeks. CONCLUSION: CIS could be a useful index for mortality risk prediction and is potentially applicable as a severity scoring system for individual patients with MOF.