One pathophysiological sign of sarcopenia is chronic inflammation. Given that levels of red blood cell distribution width (RDW) are increased in chronic inflammation, we evaluated the association between increased RDW and sarcopenia among adults in the general U. S. population and analyzed data from 11,761 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Sarcopenia was defined as an appendicular skeletal muscle mass (ASM) divided by weight (%) that was less than one standard deviation (SD) below the mean of young adults. The odds ratios (ORs) and confidence intervals (CIs) for sarcopenia were calculated across RDW quartiles after adjusting for confounding factors. Elevated RDW levels were significantly associated with sarcopenia after adjusting for age, sex, race, education, household income, smoking, physical activity, hypertension, diabetes, cardiovascular disease, C-reactive protein, and hemoglobin (OR of highest quartile: 1.72 (95% CI: 1.43, 2.06)). Further, in a model stratified by obesity, an elevated RDW was associated with sarcopenia in the overweight and obese group, but not in the normal weight group. Our study shows that elevated RDW is associated with sarcopenia, and this association is particularly strong in people who are overweight and obese.