BACKGROUND: Obesity is associated with a variety of cardiovascular, pulmonary, and skeletal muscle aberrations that negatively affect physical fitness and other metabolic parameters. However, it is unclear whether these impairments are exacerbated in lifelong obesity. OBJECTIVE: We aimed to examine how age of obesity onset (childhood versus adult) affects cardiorespiratory fitness (CRF), handgrip strength, resting metabolic rate (RMR), and substrate oxidation in adults. METHODS: We recruited 31 adults (BMI 29.5 to 39.4 kg/m2) who had either developed obesity before puberty (childhood-onset [CO]; n=13) or after the age of 18 (adult-onset [AO]; n=18). CRF was measured using the YMCA submaximal bike test and handgrip strength was measured using handgrip dynamometry. RMR and substrate oxidation was measured using indirect calorimetry. RESULTS: Mean handgrip strength (±SD) was lower in adults with childhood- versus adult-onset obesity (CO: 56 ± 10 vs. AO: 72 ± 20 kg; p = 0.01). Fat oxidation was also lower in the childhood-onset group (CO: 51.07 ± 18.39 vs. AO: 67.55 ± 23.83 mg/min; p = 0.04), while CRF, RMR and carbohydrate oxidation were not different between groups (p > 0.05). These results persisted when adjusting for age, sex, and body composition. CONCLUSION: Our results show that persistent obesity since childhood impairs muscle strength and fat oxidation, but not RMR and CRF, compared to adult-onset obesity. These results suggest that maintaining a healthy body weight early in life may delay the loss of muscle strength and impairment in fat oxidation in later life and help prevent future disease.