Chloride is the major extracellular anion. Its precise function in the body is not well understood; however, it is involved in maintaining osmotic pressure, proper body hydration, and electric neutrality. In the absence of acid-base disturbances, chloride concentrations in plasma will generally follow those of sodium (Na+). Since urine is the primary mode of elimination of ingested chloride, urinary chloride excretion during steady state conditions will reflect ingested chloride, which predominantly is in the form of sodium chloride (NaCl). However, under certain clinical conditions, the renal excretion of chloride may not reflect intake. For instance, during states of extracellular volume depletion, urine chloride (and sodium) excretion is reduced.

In normal individuals, serum chloride values vary little during the day, although there is a slight decrease after meals due to the diversion of chloride to the production of gastric juice.