To evaluate if low plasma vasopressin and high norepinephrine concentrations predict grave prognosis of sepsis, a prospective sample of consecutive patients visiting the emergency department of a university teaching hospital who met the American College of Chest Physicians criteria of sepsis or severe sepsis was enrolled. Besides septic workup, we measured serum vasopressin and norepinephrine concentrations to correlate the impending outcome. One hundred eighty-two patients aged 27 to 99 years met the inclusive criteria and were classified as those with septic shock (n = 72), severe sepsis (n = 56), and those with sepsis only (n = 54) according to the outcome within 6 hours. Thirty healthy subjects were included as control. The plasma vasopressin level at baseline was significantly lower for those who finally developed septic shock (septic shock group, 3.6 ± 2.5 pg/mL; 95% confidence interval [CI], 3.0-4.2 pg/mL; severe sepsis group, 21.8 ± 4.1 pg/mL, 95% CI, 20.7-22.9 pg/mL; sepsis group, 10.6 ± 6.5 pg/mL, 95% CI, 8.8-12.4 pg/mL, P < .001), whereas the norepinephrine level was highest for the same group (septic shock group, 3650 ± 980 pg/mL, 95% CI, 3420-3880 pg/mL; severe sepsis group, 3600 ± 1000 pg/mL, 95% CI, 3330-3870 pg/mL; sepsis group, 1720 ± 320 pg/mL, 95% CI, 1630-1810 pg/mL). The vasopressin/norepinephrine ratio was significantly lower for the patients with final diagnosis of septic shock (P < .001). The mean interval between the time of samples drawn and the time of the most severe occurring sequelae was 2.4 ± 0.8 hours. Receiver operating characteristic analysis revealed that the vasopressin/norepinephrine ratio 1 × 10⁻³ had a sensitivity of 97% (95% CI, 90%-99%) and a specificity of 85% (95% CI, 78%-91%) for detecting impending septic shock. Low serum vasopressin/norepinephrine ratio can predict impending septic shock.