This prospective study was aimed to test the hypothesis that tissue hemoglobin oxygen saturation (StO₂) measured noninvasively using near-infrared spectroscopy is a reliable indicator of global oxygen delivery (DO₂) measured invasively using a pulmonary artery catheter (PAC) in patients with septic shock. The study setting was a 26-bed medical-surgical intensive care unit at a university hospital. Subjects were adult patients in septic shock who required PAC hemodynamic monitoring for resuscitation. Interventions included transient ischemic challenge on the forearm. After blood pressure normalization, hemodynamic and oximetric PAC variables and, simultaneously, steady-state StO₂ and its changes from ischemic challenge (deoxygenation and reoxygenation rates) were measured. Fifteen patients were studied. All the patients had a mean arterial pressure above 65 mmHg. The DO₂ index (iDO₂) range in the studied population was 215 to 674 mL O₂/min per m. The mean mixed venous oxygen saturation value was 61% ± 10%, mean cardiac index was 3.4 ± 0.9 L/min per m, and blood lactate level was 4.6 ± 2.7 mmol/L. Steady-state StO₂ significantly correlated with iDO₂, arterial and venous O₂ content, and O₂ extraction ratio. A StO₂ cutoff value of 75% predicted iDO₂ below 450, with a sensitivity of 0.9 and a specificity of 0.9. In patients in septic shock and normalized MAP, low StO₂ reflects extremely low iDO₂. Steady-state StO₂ does not correlate with moderately low iDO₂, indicating poor sensitivity of StO₂ to rule out hypoperfusion.