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Background: Exploring a biomarker with enhanced sensitivity and specificity for tissue perfusion may facilitate the timely identification of circulatory collapse, and enable more precise resuscitation efforts. Objective: The objective of this study was to ascertain the correlation between whole blood lactate versus plasma renin concentration being a biomarker of tissue perfusion and predictor of mortality among hypotensive critically ill patients. Methods: This prospective, observational cohort study enrolled 84 hypotensive critically ill patients. Plasma renin concentration and blood lactate were measured at enrollment, 24, 48, and 72 hours. The primary outcome is the correlation between the recorded renin, lactate concentrations and mortality rate during hospitalization. Results: The mean plasma renin concentration at enrollment was 61.95 pg/ml in survivors, and 104.45 pg/ml in non-survivors (p = <0.001). The non-survivors exhibited a significant boost in plasma renin concentration after 48 and 72 hours, opposed to the survivors (112 vs 40.89, and 106.64 vs 28.85 pg/ml) respectively. There was a significant positive correlation between plasma renin, blood lactate concentrations and patient mortality (r = 0.389 & 0.601) respectively. Conclusion: Plasma renin and whole blood lactate had positive correlation to mortality, yet plasma renin revealed superior diagnostic accuracy over blood lactate for mortality prediction in hypotensive critically-ill patients. Trial registration: The protocol of this study can be obtained on ClinicalTrials.gov with the id NCT05810415. [ABSTRACT FROM AUTHOR]