The relative impact of motor- and non-motor symptoms on health-related quality of life in early Parkinson's disease is poorly documented.188 patients with incident Parkinson's disease from a population-based study were examined at the time of diagnosis, before initiation of dopaminergic treatment, with follow-up of 166 patients three years later. Health-related quality of life was assessed by the 36-item Short-form Health Survey (SF-36). Motor and non-motor variables were derived from the Unified Parkinson's disease rating scale and other established scales.Multiple regression analyses showed that the non-motor symptoms strongest associated with reduced SF-36 scores at diagnosis and three years later were depression, fatigue and sensory complaints. The motor symptoms most related to impaired SF-36 scores were problems with gait and activities of daily living that cover personal needs. The variance of SF-36 mental summary scores was much better explained by non-motor vs. motor symptoms, both at baseline (R(2) = 0.384 vs. 0.095) and 3 years later (R(2) = 0.441 vs. 0.195). Also SF-36 physical summary scores were better explained by non-motor vs. motor symptoms with R(2) = 0.372 vs. 0.322 at baseline and R(2) = 0.468 vs. 0.315 after 3 years.In early PD, including the phase before dopaminergic treatment is initiated, non-motor symptoms are more important for reduced health-related quality of life than motor symptoms. Fatigue, depression, sensory complaints and gait disturbances emerge as the most relevant symptoms and should be given corresponding attention in the management of patients with early PD.