Individuals from low socioeconomic backgrounds are disproportionately affected by the burden of cardiovascular disease (CVD), yet data regarding risk factors in this population are lacking, particularly regarding emerging biomarkers of CVD such as C-reactive protein (CRP). We measured high-sensitivity CRP and examined its association with demographic and lifestyle factors in a sample of 792 participants aged 40-79 years from the Southern Community Cohort Study, which has an over-representation of socioeconomically disadvantaged individuals (over 60% with a total annual household income < USD15,000). We found that within this population the prevalence of elevated CRP (>3 mg/L) varied significantly by sex, race, smoking status, and body mass index (BMI). The multivariable-adjusted prevalence odds ratios (ORs) (95% CIs) for having elevated CRP were 1.6 (1.1-2.3) for women vs. men, 1.4 (0.9-2.0) for African Americans vs. whites, 2.3 (1.4-3.8) for African American women vs. white men, 1.8 (1.2-2.7) for current smokers vs. non-smokers, and 4.2 (2.7-6.6) for obese (BMI 30.0-44.9 kg/m;{2}) vs. healthy-weight (BMI 18.3-24.9 kg/m;{2}) participants. Further stratified analyses revealed that the association between BMI and elevated CRP was stronger among African Americans than whites and women than men, with prevalence ORs (95% CI) comparing obese vs. healthy-weight categories reaching 22.8 (7.1-73.8) for African American women. In conclusion, in this socioeconomically disadvantaged population, sex, race, smoking, and BMI were associated with elevated CRP. Moreover, inflammatory response to obesity differed by race and sex, which may contribute to CVD disparities.