Objectives There is scarce data about effects of treatment of clinical depression in peritoneal dialysis (PD) population. We aimed to determine prevalence of depression, its association with health-related quality of life (HRQoL) and effects of sertraline treatment in PD patients. Materials and methods We included 124 PD patients who had been on PD at least for 6 months. Short Form of Medical Outcomes Study was used to evaluate HRQoL. Depression was screened by Beck Depression Inventory (BDI). Patients with a BDI score ≥17 were deemed to have depression and were referred to a psychiatrist for evaluation via Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) of diagnosis of clinical depression. About 25 patients diagnosed with clinical depression agreed to receive antidepressant treatment (Sertraline hydrochloride, 50 mg/day) for a 12-week period. After the treatment, biochemical analyses and questionnaires were repeated. Results Thirty-two patients (25.8%) had depression. BDI score of patients were lower compared to those without depressive symptoms (23 ± 6.7 and 9.8 ± 3.0, respectively P<0.001). Physical component scale (PCS) and mental component scale (MCS) domains of HRQoL were significantly decreased in patients with depression than in patients without depression (P<0.001 for PCS and MCS). In bivariate analysis the BDI score was correlated inversely with the PCS and MCS (P<0.001). Sertraline treatment improved BDI score of patients with depression (P<0.001). HRQoL parameters also improved. No adverse effects requiring drug cessation was seen in the study group. Conclusions Treatment of depression with sertraline is associated with improvement of the HRQoL and symptoms related to depression. © Springer Science+Business Media, B.V. 2009.