Background: The Henderson-Hasselbalch equation is used in the conventional assessment of acid-base status. In 1983, P. Stewart put up an alternate strategy. The Henderson-Hasselbalch equation uses variations in PCO2 and bicarbonate to explain the acid-base state. On the other hand, the Stewart theory states that albumin, inorganic phosphate, PCO2, Strong Ion Difference (SID), and SID dictate acid-base status. Therefore, these variables have an important role in clinical management. The metabolic acidosis caused by unmeasured anions is accurately identified by the Stewart physiochemical approach, and it is a predictor of mortality in patients with leptospirosis. Aims and Objectives: Comparison of the leptospirosis patient’s S. albumin (requiring ABG analysis) and arterial blood gas (ABG) analysis parameters (pH, PO2, PCO2, HCO3-, BE, SaO2, S.Na+, S.K+, S.Cl, S.PO43-, and anion gap) to compare the conventional and Stewart methods and determine the type of acid-base disturbances present in leptospirosis patients in the intensive care unit. Materials and Methods: Following approval by the ethics committee, ABG and S. Albumin were taken from the clinical notes of fifty patients. The Henderson-Hasselbalch equation, in its conventional form, was unable to identify complex acid-base problems. Thus, we integrated this with the Stewart method. Results: The majority of leptospirosis patients had a mixed disorder characterized by respiratory alkalosis, metabolic acidosis, and metabolic alkalosis. The most prevalent conditions were metabolic acidosis, respiratory alkalosis, and metabolic alkalosis. Stewart’s method can help explain the cause of metabolic disorders. Stewart’s approach also made occult acid-base disorders visible. Conclusion: Stewart’s approach emphasizes the significance of Na+, K+, Cl-, Alb, and PO43- and clarifies their part in the development of metabolic abnormalities, particularly those involving Alb and PO43-. This demonstrates unequivocally that the cause of the metabolic abnormalities can be explained by Stewart’s method, which is highly helpful in planning the management.