Metabolic acidosis is very common in critically ill septic patients. Acidosis may be a result of the underlying pathophysiology, but it also may be the result of the way in which those patients are managed. Chloride-associated acidosis is frequent and is potentially aggravated during fluid resuscitation. The severity of metabolic acidosis is associated with poor clinical outcomes; however, it remains uncertain whether or not there is a causal relationship between acidosis and the pathophysiology of septic syndromes. Several experimental findings have demonstrated the impact of acidosis modulation on the release of inflammatory mediators and cardiovascular function. Treatment of metabolic acidosis is based on control of the underlying process and support of organ dysfunction, although the use of intravenous chloridepoor balanced solutions seems an attractive option to prevent the worsening of metabolic acidosis during fluid resuscitation.