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Objective This study investigated the factors related to the ratio of the venoarterial carbon dioxide tension difference [P(v-a)CO 2 ] to the arteriovenous oxygen content difference [C(a-v)O 2 ] (hereafter termed “Ratio”). Methods We retrospectively studied 1294 pairs of arterial and central venous blood gas measurements in 352 critically ill patients. A high Ratio was defined as > 1.68 based on published literature. Measurements were divided into four groups: Group I [P(v-a)CO 2  ≤ 6 mmHg/central venous oxygen saturation (ScvO 2 ) < 70%], Group II [P(v-a)CO 2  ≤ 6 mmHg/ScvO 2  ≥ 70%], Group III [P(v-a)CO 2  > 6 mmHg/ScvO 2  ≥ 70%], and Group IV [P(v-a)CO 2  > 6 mmHg/ScvO 2  < 70%]. Results The Ratio’s strongest correlation was with P(v-a)CO 2 when compared with ScvO 2 and hemoglobin in all data. The P(v-a)CO 2 and ScvO 2 were significantly higher and the hemoglobin and arterial oxygen saturation were significantly lower in the high Ratio measurements (>1.68) than low Ratio measurements (≤1.68). The P(v-a)CO 2 was best for predicting a high Ratio. A P(v-a)CO 2 threshold of 7 mmHg was associated with a sensitivity of 41.77% and specificity of 90.62% for predicting a high Ratio. Conclusions A high P(v-a)CO 2 is the most relevant contributor to a high Ratio among all related factors in critically ill patients.