Aim of this study was to determine the predictors of caregiver burden among spouse caregivers of patients with Parkinson's disease (PD). Forty consecutive PD patients and their spouse caregivers were included. Patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr scale (HY), the Mini-Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI), and the Geriatric Depression Scale (GDS). Stress and depressive symptoms among caregivers were evaluated using the Caregiver Burden Inventory (CBI) scale and the GDS. Only PD severity (HY) and mental symptoms (NPI) were significantly associated to caregiver distress. A major attention must be given to the early identification of factors generating stress in caregivers in order to improve caregiver quality of life and patient's care.