Findings of post-acute sequelae of Post-COVID Conditions (PCC) manifestations of fatigue, pain, dyspnea, and muscle weakness, provide a strong rationale for rehabilitation; yet few formal studies exist and the effects of severe acute respiratory syndrome coronavirus-2 infection on function are not well described. Notably, two- thirds of Veterans are overweight and obese, rendering excess adiposity a significant risk factor and a high- priority area related to PCC prevention and care. Obesity increases the risk of severe illness in Veterans recovering from PCC, but how it does so is not fully understood. Recent research suggests that excess adipose tissue is associated with adverse changes in adipose cellular function, and that these variations may be involved in the biology of aging and the etiology of aging- related diseases. Adipose tissue contains cells that have undergone cellular senescence, which induces inflammation, cytotoxicity, and metabolic dysfunction in other cells and tissues. However, the precise role of adipose tissue cellular composition on PCC recovery is limited. Thus, we propose to evaluate the role of obesity and PCC on physical functioning, health-related quality of life (HRQOL), and systemic and adipose tissue inflammatory and cellular senescence profiles in ethnically diverse older Veterans from the Audie Murphy (San Antonio) and Baltimore VA Medical Centers. Further, we propose a randomized controlled trial to determine whether a reduction in body weight and increased physical function by a weight loss intervention (WL), including dietary modification and exercise, in obese Veterans with PCC will reduce systemic and adipose tissue inflammation and senescence, which will have important implications for PCC recovery. We will pursue the following aims: Aim 1: To compare physical function, body composition, HRQOL, PCC symptoms, and adipose tissue molecular profiling in four cohorts of Veterans at baseline: lean PCC naïve, lean with PCC, obese PCC naïve, and obese with PCC (N=150). Aim 2: To compare in Veterans with obesity: a) a 12-week randomized WL vs. weight stability (WS) intervention (30/group) on physical function, body composition, HRQOL, and PCC symptoms together with changes in the global molecular profile in adipose tissue in Veterans with PCC and b) the WL intervention in PCC naïve vs. with PCC (N=30/group) on these outcomes. Older (55-80 years) men and women Veterans will be recruited. We will perform a standard functional battery (maximal aerobic capacity [VO2max; primary outcome], usual gait speed, six min walk distance, timed up and go, and handgrip strength), body composition (dual energy x-ray absorptiometry and computed tomography scans), HRQOL (NIH PROMIS-57), and PCC symptoms (COVID-19 Yorkshire Rehabilitation Scale [C19-YRS]) and adipose tissue will be collected. Further, we will test, in a randomized controlled trial, the hypothesis that a WL intervention, compared to weight stability (WS), improves p...