© 2018 The Author(s) Objective: To measure changes in range of motion (ROM) over time in a cohort of 55 adolescents and young adults with chronic fatigue syndrome and to determine whether changes in ROM correlated with changes in health-related quality of life. Study design: Participants underwent a standardized examination of 11 areas of limb and spine ROM at baseline and at 3- to 6-month intervals for 2 years, resulting in a ROM score that ranged from 0 (normal throughout) to 11 (abnormal ROM in all areas tested). We measured the time until the ROM score was ≤2 (the score in healthy age-matched controls). Change in ROM was measured by subtracting the 24-month from the baseline ROM score and by summing the degrees of change in the 10 tests with continuous outcomes. Health-related quality of life was measured using the Pediatric Quality of Life Inventory 4.0 (PedsQL). Results: The mean age at enrollment was 16.5 years (range 10-23). Two-year follow-up was available for 53 (96%). The proportion with a ROM score of >2 fell gradually over 2 years, from 78% at entry to 20% at 24 months (P <.001). ROM scores improved from a median of 5 at entry to 2 at 24 months (P <.001). The change in the summed degrees of improvement in ROM correlated positively with improvement in the PedsQL physical function subscale (r = 0.30; P <.03). Conclusions: In association with multimodal therapy, young people with chronic fatigue syndrome experienced progressively less impairment in ROM over 2 years, correlating with improvements in the physical function subscale of the PedsQL.