Abstract: The aim of this study was to evaluate the status of serum IL-1b and TNF-α in depressed patients who treated or non-treated or poisoned with tricyclic antidepressants (TCAs) in comparison to healthy subjects. In this prospective comparative study, patients were selected from those admitted at Loghman-Hakim Hospital from August 2007 to January 2008. Serum level of IL-1b and TNF-α were compared among group of subjects (10 in each) of healthy subjects, TCA-poisoned patients, TCA-treated depressed patients and non-treated depressed patients. Demographic and clinical data were collected by a questioner filled out by a trained practitioner in daily clinical management. Blood was tested for liver function, blood cells, electrocardiography and arterial blood gases. Complete blood analysis and demographic data did now show significant change between groups. IL-1b level was higher among females. The group of depressed patients non-treated with TCAs showed higher serum levels of IL-1b and TNF-α than other groups. No significant difference was observed in IL-1b and TNF-α values among healthy control, depressed TCA-treated and TCA-poisoned groups. It is concluded that depression and gender may influence the production of cytokines while neither TCAs treatment nor its overdose affect IL-1b and TNF-α.