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Fluoxetine, a widely used antidepressant, can affect the serum sodium level. The aim of this study was to evaluate and compare changes in the serum sodium level of depressive patients taking fluoxetine according to age.This quasi-experimental study was conducted on 126 patients with depression, dividing the patients into two age groups of 15 to 35 years, and above 55 years, who referred to psychiatric clinics of the Isfahan University of Medical Sciences. Serum sodium level was measured prior to fluoxetine therapy and at the first and third week after; adverse symptoms were recorded. Serum sodium level, hyponatremia, and other adverse effects were compared between the two age groups.There was a significant decrease in serum sodium levels in the older patients at the first and third week after the therapy; but the serum sodium levels decreased only after the third week of therapy in the younger patients (p