Wolff-Parkinson-White (WPW) syndrome is a congenital disorder characterised by a macro-reentrant arrhythmia caused by preexcitation of the ventricles. A significant proportion of cases are detected incidentally in asymptomatic patients during routine checkups. Because little is known about the use of selective serotonin reuptake inhibitors in youths with preexisting cardiac disease, we report here a 15-year-old adolescent with asymptomatic WPW syndrome and severe depressive symptoms. An improvement in depressive symptoms was observed with sertraline therapy and the absence of cardiac adverse effects after 5 months of treatment suggested that sertraline could be used at therapeutic doses in adolescents with preexisting but asymptomatic WPW syndrome.