Some research has supported differences in mood functioning in patients with Parkinson's disease (PD) whose motor symptoms begin at the left or right hemibody. Also, a relationship between disease duration and mood disturbances has been reported, but only for PD patients with right hemibody onset. There have been no investigations reported examining the potential interactions between side of onset of motor symptoms, mood, and disease duration on cognitive functioning. Hence, the purpose of this investigation was to determine whether the interaction between mood and disease duration differentially affects cognitive functioning in patients with PD whose motor symptoms begin at the left and right hemibody. A total of 33 PD patients with left hemibody onset and 29 PD patients with right hemibody onset were given a battery of tests to evaluate mood functioning and general cognitive functioning. As predicted, the results indicated that the interaction of disease duration and mood significantly predicted cognitive functioning for PD patients with right hemibody onset of symptoms but not for PD patients with left hemibody onset of symptoms. Interestingly, an unexpected finding was a significant positive relationship between disease duration and energy level for patients with left hemibody onset but not for patients with right hemibody onset. These results indicate that mood problems and disease duration interact to significantly affect cognitive functioning but only for those PD patients who experience a right hemibody onset of symptoms. © 2013 Copyright Taylor and Francis Group, LLC.