Evidence regarding the relationship between serum vitamin C levels and human papillomavirus (HPV) infection is limited. Therefore, this study aimed to investigate whether serum vitamin C levels are independently associated with HPV infection. Data for this cross-sectional study were obtained from the National Health and Nutrition Examination Survey 2003–2006. A total of 2174 women, 18–59 years of age, were enrolled in this study. The associations between serum vitamin C levels (continuous and categorical forms) and cervicovaginal HPV infection were estimated using weighted logistic regression. The adjusted binary logistic regression showed that serum vitamin C was not associated with the risk of HPV infection after adjusting for age, race, poverty income ratio, alcohol consumption, smoking, body mass index, education, and health condition (odds ratio [OR] 0.998, 95% confidence interval [CI] 0.994–1.001). Serum vitamin C levels were converted from a continuous