Objective: To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia. Design: Retrospective register-based cohort study using nationwide registers from 1998 to 2012. Setting: The North Denmark Region. Participants: In total, 638 352 individuals were included. Primary and secondary outcome measures: Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium ( p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models. Results: An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14). Conclusions: All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine.