OBJECTIVE Previous research has examined the neurocognitive effects of depression in Parkinson's disease (PD), finding worse performance on tests of cognitive functioning in PD patients with depression as compared to those without depression. However, this research has not considered the effect of side of onset of motor symptoms. Hence, we sought to investigate the interaction between depression and side of onset on working memory in patients with PD. METHOD A total of 66 patients with PD completed the Digit Span Backward subtest of the Wechsler Memory Scale-III as well as two other tests of executive functioning. Groups of left hemibody onset (LHO) with and without depression and right hemibody onset (RHO) with and without depression were created. RESULTS The results indicated significantly lower performance on the measure of working memory for the LHO with depression group, relative to both the LHO without depression and the RHO with depression groups. CONCLUSION These findings indicate that working memory is worse in patients with LHO of motor symptoms who are also depressed, and they suggest that this group of patients might experience greater disability and lower quality of life.