Although oral contraceptives (OCs) are widely used, few national epidemiological studies have evaluated the association between OC use and serum high-sensitivity C-reactive protein (hs-CRP) levels in Korean women. This population-based cross-sectional study was conducted with data from the 2015–2018 National Health and Nutrition Examination Survey. In the sample of 5332 premenopausal women aged ≥19 years, hs-CRP concentrations were 1.087 mg/L among OC users and 0.953 mg/L among OC non-users. After adjustment for confounders, OC users had an increased likelihood of having risky (>1.0 mg/L) hs-CRP levels (adjusted odds ratio (aOR) = 1.58; 95% confidence interval (CI), 1.25–1.98) compared with OC non-users. In addition, the aOR for high-risk (>3.0 mg/L) hs-CRP levels in OC users compared with non-users was 1.51 (95% CI, 1.06–2.16). These findings demonstrate that OC use alters the concentration of hs-CRP, a biomarker of chronic low-grade inflammation, and suggest that long-term OC use is a risk factor in the pathogenesis of inflammatory diseases, including cardiovascular diseases.