Improvements in initial resuscitation efforts coupled with advancements in technological support and knowledge of disease process have improved the survival of critically ill patients and resulted in a relatively new disorder, multiple organ dysfunction/failure. In prior years, patients would have died much earlier in their disease course, long before they would develop the evidence of organ dysfunction that we now refer to as multiple organ dysfunction syndrome (MODS) or multiple organ failure (MOF).Out of the 40 patients at risk for MODS included in this study, twenty three patients developed this syndrome and twenty two of them died. Five of the seventeen patients at risk of developing MODS but not developing the syndrome died. In the patient groups reported in this study, high plasma concentrations of TNF-alpha and IL-6 were predictive during the early phase for the development of MODS and for the severity of illness and outcome. Furthermore, our results showed that a marked increase of the natural inhibitors of TNF-alpha (soluble receptors, sTNF-alpha), occurs and represents a good predictive value for development of MODS, and also showed good positive correlation with TNF-alpha. Also, we observed a good correlation between plasma TNF-alpha and IL-6 concentrations and MODS score and APACHE II score in septic patients group and poor correlation in non-septic patients group. Our data suggests that the balance between TNF-alpha and its inhibitors may play an important role in the pathogenesis of MODS. Moroever, patients developing MODS showed an increase of markers of antioxidant activity in the all stages of the disease. Patients developing MODS showed a more marked increase of both metal ions (copper and zinc) in plasma of patients developing MODS compared with patients without MODS.