Metabolic acidosis is traditionally classified into an elevated anion-gap metabolic acidosis or a non-anion-gap (hyperchloremic) metabolic acidosis. The importance of this classification is that it provides a differential diagnosis and guidance for priorities of treatment. The anion gap is the difference in charge between the sodium and the sum of the bicarbonate and chloride (Na-[Cl+HCO₃]). The normal anion gap ranges from 10 to 14. When the anion gap is elevated in a metabolic acidosis, the differential diagnosis is characterized by the mnemonic MUDPILES, which stands for methanol, uremia, diabetic ketoacidosis, paraldehyde, iron/isoniazid, lactic acidosis, ethanol/ethylene glycol, and salicylates.

A non-anion-gap metabolic acidosis is usually classified in three different ways. First, a renal tubular acidosis (RTA) must be considered and ruled out when a non-anion-gap metabolic acidosis presents itself. These disorders may be associated with either hypokalemia (proximal type II RTA) or hyperkalemia (type IV RTA). Second, a hyperchloremic metabolic acidosis may occur from the loss of fluids that are low in chloride. The most common fluids to consider are excessive stool output, drainage from pancreatic or ileostomy drains, and urinary diversions. Finally, a hyperchloremic metabolic acidosis may simply occur because of excessive administration of a chloride containing salt, such as sodium chloride, potassium chloride, or ammonium chloride. When hyperchloremia develops, the kidney exchanges bicarbonate to maintain electrical neutrality and the metabolic acidosis develops.