Objective. The PedsQL™ (Pediatric Quality of Life Inventory™) is a modular instrument designed to measure health-related quality of life (HRQOL) and disease-specific symptoms in children and adolescents. The PedsQL™ Multidimensional Fatigue Scale was designed as a child self-report and parent proxy-report generic symptom-specific instrument to measure fatigue in pediatric patients. The objective of the present study was to determine the feasibility, reliability, and validity of the PedsQL™ Multidimensional Fatigue Scale in pediatric obesity. Methods. The 18-item PedsQL™ Multidimensional Fatigue Scale (General Fatigue, Sleep/Rest Fatigue, and Cognitive Fatigue domains) and the PedsQL™ 4.0 Generic Core Scales were completed by 41 pediatric patients with a physician-diagnosis of obesity and 43 parents from a hospital-based Pediatric Endocrinology Clinic. Results. The PedsQL™ Multidimensional Fatigue Scale evidenced minimal missing responses (1.6%, child report; 0.5%, parent report), achieved excellent reliability for the Total Fatigue Scale Score (α = 0.90 child report, 0.90 parent report), distinguished between pediatric patients with obesity and healthy children, and was significantly correlated with the PedsQL™ 4.0 Generic Core Scales supporting construct validity. Pediatric patients with obesity experienced fatigue comparable with pediatric patients receiving cancer treatment, demonstrating the relative severity of their fatigue symptoms. Conclusions. The results demonstrate the measurement properties of the PedsQL™ Multidimensional Fatigue Scale in pediatric obesity. The findings suggest that the PedsQL™ Multidimensional Fatigue Scale may be utilized in the standardized evaluation of fatigue in pediatric patients with obesity.