BACKGROUND: Mitochondrial function influences Parkinson's disease (PD) through the accumulation of pathogenic alpha-synuclein, oxidative stress, impaired autophagy, and neuroinflammation. The mitochondrial DNA copy number (mtDNA-CN), representing the number of mitochondrial DNA copies within a cell, serves as an easily assessable proxy for mitochondrial function. OBJECTIVE: This study aimed to assess the diagnostic and prognostic capabilities of mtDNA-CN in PD. METHODS: We assessed mtDNA-CN in blood samples using whole genome sequencing from 405 patients with PD and 200 healthy controls (HC). We examined the relationship between mtDNA-CN levels and motor symptom severity in PD, as well as their association with dementia development in patients with early-PD (within 3 years of diagnosis). RESULTS: mtDNA-CN levels were significantly lower in patients with PD compared with HC (P = 1.1 × 10 CONCLUSION: Our findings suggest that blood mtDNA-CN may function as a diagnostic biomarker for PD and a prognostic marker for dementia in patients with PD. © 2025 International Parkinson and Movement Disorder Society.