Introduction: The evaluation of metabolism and the diagnostic classification of acid-base disorders has generated great controversy. Acid-base balance (ABB) is approached by means of the physicochemical and Henderson’s models.Objective: To compare two diagnostic approaches to ABB in patients with severe sepsis.Materials and methods: Prospective, descriptive study conducted in patients with severe sepsis. ABB was analyzed within the first 24 hours. The diagnosis was compared according to each model and the causes of the disorders were compared according to the physicochemical model.Results: 38 patients were included in the study, of which 21 (55%) were women; the mean age was 49 years, the median APACHE II, 13.28, and the mortality at 28 days, 24.3%. The traditional approach identified 8 patients with normal ABB, 20 with metabolic acidosis, and 10 with other disorders. Based on the physicochemical model, all subjects had acidosis and metabolic alkalosis. Increased strong ion difference (SID) was the most frequently observed disorder.Conclusion: The physicochemical model was useful to diagnose more patients with acid-base disorders. According to these results, all cases presented with acidosis and metabolic alkalosis; the most frequent proposed mechanism of acidosis was elevated SID. The nature of these disorders and their clinical relevance is yet to be established.