Hyperlactataemia reflects an imbalance between production and clearance of lactate. Accumulation of lactate is associated with acidosis; lactic acidosis is a high anion gap metabolic acidosis.

Aerobic glycolysis can also cause lactate accumulation, where in certain circumstances pyruvate is shunted to lactate despite adequate oxygenation. This is particularly stimulated by β2 activation due to stress, shock, adrenaline or beta 2 agonists (e.g. salbutamol). Aerobic glycolysis can also be seen in certain tumours.

Metformin causes reduced gluconeogenesis, which in the presence of renal failure can lead to lactate accumulation. Certain inherited or acquired conditions can cause hyperlactataemia though impaired pyruvate dehydrogenase inhibition; this is most relevant in sepsis and thiamine deficiency.

Hepatic dysfunction may cause lactate accumulation due to impaired clearance, though this does not typically occut until hepatic blood flow drops below 25%.