Objective To explore the relationship between central venous-to-arterial carbon dioxide difference/arterial-to-venous oxygen difference ration [P(cv-a)CO2/C(a-cv)O2] and arterial lactate in patients with sepsis. Methods A retrospective analysis was carried on 36 septic patients who were admitted to the Intensive Care Unit of Nanjng Drum-tower Hospital affiliated to Medical School of Nanjing University from May 2013 to November 2013. Cardiac index was measured by transpulmonary thermodilution. At the same time, femoral artery and central venous blood were collected to measure the value of arterial lactate and central venous oxygen saturation (ScvO2) by blood gas analysis and calculate central venous-to-arterial carbon dioxide difference [P(cv-a)CO2], arterial-to-venous oxygen difference [C(a-cv)O2], and their ration [P(cv-a)CO2/C(a-cv)O2], oxygen delivery (DO2) and oxygen consumption (VO2). The subjects were divided intoahyperlactatemia group (≥2 mmol/L) andanormal lactate group (< 2 mmol/L) according to arterial lactate value. P(cv-a)CO2/C(a-cv)O2 and other oxygen metabolism parameters were compared between two groups. Receiver operating characteristic (ROC) curve was used to evaluate the accuracy of P(cv-a)CO2/C(a-cv)O2 and other parameters for diagnosis of hyperlactatemia. Results A total of 36 patients with 119 data were collected. Compared with the normal lactate group, P(cv-a)CO2/C(a-cv)O2 was significantly higher [(1.38±0.76)mm Hg/mL vs. (2.31±1.01) mm Hg/mL, P < 0.01], ScvO2, DO2 and VO2 were significantly lower in the hyperlactatemia group [ScvO2: (74.26±9.13)% vs. (70.29±9.72)%; DO2: (505.52±208.39) mL/(min·m2) vs. (429.98±173.63) mL/(min·m2)]; VO2: (129.01±54.94) mL/(min·m2) vs. (109.99±38.79) mL/(min·m2), P < 0.05]. P(cv-a)CO2 had no significant difference between two groups [(5.76±3.70) mm Hg vs. (6.59±3.70) mm Hg, P > 0.05]. P(cv-a)CO2/C(a-cv)O2 was positively correlated with lactate (r=0.646, P < 0.01). ScvO2 was negatively correlated with lactate (r=-0.277, P < 0.01). DO2 and VO2 had no significant correlation with lactate (P > 0.05). The area under ROC curve (AUC) of P(cv-a)CO2 /C(a-cv)O2 for diagnosis of hyperlactatemia was 0.820, with 95% confidence interval (95%CI) of 0.715 - 0.925(P < 0.001); The AUC of ScvO2 was 0.622, with 95%CI of 0.520 - 0.724(P=0.025). Conclusion Compared with the traditional oxygen metabolism parameters, P(cv-a)CO2/C(a-cv)O2 can accurately diagnose hyperlactatemia, and isareliable parameter to reflect oxygen metabolism in patients with sepsis.