Chloride is the most abundant extracellular anion. Together with natrium-chloride is responsible for the maintenance of osmotic pressure, the anion-cation balance and therefore of the water distribution in the extracellular fluid compartment.Decreased plasma Cl—concentrations (hypochloremia) can result from salt-losing nephritis, persistent gastric secretion, prolonged vomiting and metabolic acidosis that are caused by increased production or reduced secretion of organic acids. Increased plasma Cl--concentrations (hyperchloremia) occur with dehydration, renal tubular acidosis, acute renal failure, in adrenocortical hyperfunction , salicylate intoxication and metabolic acidosis associated with prolonged diarrhoea and loss of sodium bicarbonate.

Chloride is often analyzed in combination with natrium and kalium to determine the anion gap in serum and/or urine. The urinary anion gap is useful in the initial evaluation of hyperchloremic metabolic acidosis.Due to the different reactivity equivalents of chloride and bromide the thiocyanate method is less disturbed by the presence of bromide than measurement with an ionselective electrode.