In Post-COVID-19 syndrome, muscle pain and fatigue are among the most common symptoms in subjects who require hospitalization by SARS-CoV2. Musculoskeletal disorders from interrelated factors such as age, previous metabolic and inflammatory diseases, hypoxia, immobilization, mechanical ventilation,malnutrition, and use glucocorticoid. HMB (?-hydroxy-?-methylbutyrate) increase protein synthesis resulting in improved muscle size and strength. Objective: to evaluate the effect of HMB supplementation on skeletal muscle mass index (SMMI), and muscle functionality in subjects with POS-COVID-19 syndrome. Materials and methods: A randomized clinical trial, subjects with previous hospitalization COVID-19 syndrome with dynapenia or muscle depletion were included. Subjects with cancer, HIV, nutritional supplementation,GFR<30 mL/min/1.73m2 or rheumatoid arthritis were excluded. The intervention group received 4 g/day of HMB for 1.5 months. (SMMI) were assessed by bioelectrical impedance and muscular functionality by functional capacity by chair test and dynamometry. Results: Thirty subjects were randomized in the intervention group (n=15) and control group (n=15);.After 1.5 months, the intervention group increased SMMI (0.73±1.2kg/m2 p= 0.048), and both groups improved hand strength, 2.1 ± 3.03 kg in the intervention group and 4.2 ± 4.3 in the control group. Conclusion: HMB improves SMMI in patients with Post-COVID-19 syndrome.