Despite the potential detrimental effects of systemic inflammation on muscle mass, which is mainly observed in patients with pathologic diseases, its role in muscle strength, especially in a healthy general population reflecting subclinical low-grade inflammation, is unclear. This is a nationally representative population-based, cross-sectional study from the Korea National Health and Nutrition Examination Survey, which enrolled 1,036 men aged ≥50 years and 1,080 postmenopausal women. After adjustment for confounders, serum high-sensitivity C-reactive protein (hsCRP) level was inversely associated with hand grip strength (HGS) in men. Consistently, compared with men in the lowest serum hsCRP quartile, those in the highest quartile showed a significant lower HGS, with a linear decrease of HGS across increasing serum hsCRP quartiles. Men with low muscle strength had 74.2% higher serum hsCRP than those without, and each standard deviation increment in serum hsCRP was associated with a multivariate-adjusted odds ratio of 1.35 for the risk of low muscle strength in men. However, these associations were not statistically significant in women. These findings provide clinical evidence that chronic subclinical low-grade inflammation may contribute to the deterioration of muscle strength seen with aging, especially in men.