Microcirculation disturbances imply poor prognosis in septic shock. Microvascular reserve can be assessed by oximetry-derived Perfusion Index (PI) after vascular occlusion test (VOT). We investigated the relationship between PI during VOT, hyperlactatemia and mortality in septic shock and the role of adrenergic stimulus in these findings. The tests were performed in 106 patients within 24 h after admission. PI was evaluated before/after 03-min flow occlusion. Peaks of PI (ΔPI peak) and time-to-peak were evaluated. PI was also evaluated in hyperemic phases derived by mechanosensitive (ΔPI0-60) and metabolic mechanisms (ΔPI60-120). We compared nonsurvivors with survivors and patients with lowest and highest ΔPI peaks, divided by 50th percentile. ΔPI peak was evaluated in presence/absence of hyperlactatemia. A correlation test between ΔPI peaks and noradrenaline doses and an assessment after doses increasing were also performed. The ΔPI peak values were higher in nonsurvivors [79% (47%-169%) vs. 48% (25%-85%); P=0.003] although peaks were reached slower in nonsurvivors. ΔPI0-60 was similar between groups [-12% (-42% to 28%) vs. 01% (-16%-23%); P = 0.211]. However, ΔPI60-120 was higher in nonsurvivors [49% (29%-84%) vs. 31% (12%-65%); P = 0.035]. Additionally, the group with higher ΔPI peaks had higher mortality than those with lower peaks [HR 2.25 (95% CI = 1.32-4.14); P = 0.003]. Mortality was extremely high in the presence of hyperlactatemia. ΔPI peaks were positively correlated with noradrenaline doses and increased after increasing doses.In conclusion, high values of PI during VOT indicate higher mortality in septic shock and are associated with adrenergic stimulus. Additionally, the assessment of PI-VOT appears to improve the predictive value of arterial lactate.