To assess the influence of parity, as a proxy for exposure to children, and sexual history on cytomegalovirus (CMV) seroprevalence.Data were retrospectively analyzed from women aged 20–49 years who were tested for CMV immunoglobulin G antibodies in the 1999–2004 National Health and Nutrition Examination Survey, a nationally representative survey of the US population. Logistic regression was used to determine independent variables associated with CMV seroprevalence.Among 3710 women, the age-adjusted CMV seroprevalence was 61.3% (95% CI 58.9%–63.6%). In age-adjusted univariate analysis, women who had given birth at least once had higher overall CMV seroprevalence (66.0%, 95% CI 63.1%–68.9%) than did those who had not given birth (49.0%, 95% CI 44.4%–53.7%; P<0.001). In multivariate logistic analysis, higher CMV seroprevalence was independently associated with number of live births (each additional birth: adjusted odds ratio [aOR] 1.2, 95% CI 1.1–1.3), age at first sexual intercourse (<18 vs ≥18years: aOR 1.3, 95% CI 1.1–1.6), lifetime sexual partners (≥10 vs <10: aOR 1.4, 95% CI 1.1–1.9), and herpes type 2 seropositivity (aOR 1.9, 95% CI 1.5–2.6) after controlling for age, race/Hispanic origin, place of birth, poverty index, and education.Among US women of reproductive age, parity and sexual exposures were independently associated with increased CMV seroprevalence.