Background: Oxygen (O2) cost of walking is a physiological marker of walking dysfunction and reflects the amount of O2 consumed per kilogram of body weight per unit distance walked. The onset of walking dysfunction (i.e., reduced walking speed and shorter stride length) is commonly observed in Parkinson's disease (PD), even in the early stages of the disease. However, the O2 cost of walking has not been assessed in persons with PD. Research question: Does O2 cost of walking differ between persons with PD and controls matched by age and sex? Methods: The sample included 31 persons with mild-to-moderate PD (Hoehn and Yahr stages 2–3) and 31 age- and sex-matched controls in this cross-sectional study. O2 consumption (VO2) was measured using a portable indirect calorimetry system during a 6-min period of over-ground walking at a normal comfortable speed, and the O2 cost of walking was calculated based on the ratio of net relative VO2 (ml kg−1 min−1) and speed (m min−1). Results: There were no differences in resting VO2, steady-state VO2, and over-ground walking speed between persons with PD and controls (p > 0.05). There was a significant difference in the O2 cost of walking between persons with PD and healthy controls (p < 0.01) such that persons with PD had a higher O2 cost of walking. The mean(SD) O2 cost of walking for persons with PD was 0.179 (0.038) ml kg−1 m−1, and the O2 cost of walking for healthy controls was 0.153 (0.024) ml kg−1 m−1. Significance: Persons with PD demonstrated a higher O2 cost of walking compared with controls, and this may reflect worse walking economy in PD. The possibility of worse walking economy under free-living conditions may result in reduced community ambulation and participation.