Introduction: The early identification and scrupulous monitoring of tissue dysoxia can improve the management of critically-ill patients. In this light, the final product of aerobe and anaerobe metabolism (that is, carbon dioxide) can provide useful information on adequacy of tissue perfusion and metabolism (9,10). The aim of our study was to evaluate whether the venous-arterial PCO2 gradient provides useful information on tissue dysfunction in patients admitted to the ICU. Methods: We prospectively studied 50 patients admitted to ICU in 2012/2013 with length of stay (LOS) >24 hours. A sample of arterial and venous blood was taken for gas analysis at admission. Venous-arterial PCO2 gradient (ΔpCO2), organ dysfunction in the first 24 hours and ICU mortality were collected. Organ dysfunction was defined as a SOFA score ≥ 2 for each organ. The patients, whether ventilated or not, were subdivided and compared on the basis of ΔpCO2 value: ΔpCO2 ≥ 6 mmHg (Higher group) and ΔpCO2 <6 mmHg (Normal group). Results: Twenty-nine patients (58%) showed a ΔpCO2 ≥ 6 mmHg (Higher group) and twenty-one patients (42%) showed a ΔpCO2 ≤ 6 mmHg (Normal group).The Higher group showed a larger rate (34%) of cardiovascular dysfunction than the Normal group (8%)(P< 0.05). Respiratory dysfunction was observed in 54% of the patients of the High group and only in 32% of the Normal group. Similarly, renal dysfunction was also slightly larger in the Higher group (26%) than in the Normal group (20%) (P > 0.05). As expected, patients of Higher group showed more complications (52%) than Normal group (32%) (P > 0.05) and ICU mortality (40%) three times larger than Normal group (12%) (P < 0.05). Conclusions & Recommendations: Despite its limitations , The above data support the hypothesis that ΔpCO2 can provide useful information on the tissue perfusion and metabolism in ICU patients and can be used as a reliable biomarker for early prediction of organ dysfunction and outcome in critically-ill patients. But, further studies on a larger number of patients are needed to confirm its reliability. Limitations : Our study was done on a small sample size and based on a pre-defined set of study parameters, which might not have reflected the true nature of general changes observed in sepsis.