Objective: Our objective was to explore the association between poor sleep quality and hs_CRP in an adult U.S. population. Methods: This study focused on 9,317 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005-2008 who were aged 20-85 years, completed a sleep disorder questionnaire, and had available information on serum hs_CRP. Sleep quality was classified into three categories (good, moderate, poor) based on the responses of participants to the NHANES sleep disorder questionnaire. High CRP was defined as hs-CRP > 1 md/dL. Linear regression model was applied to investigate the association between poor sleep quality and log-transformed hs_CRP. And logistic regression model was fitted to evaluate the association between sleep quality and the risk of high CRP. Results: Females were more likely to report poor sleep quality than males (26% vs. 19%, p<0.0001). Each sleep disorder was significantly associated with increased hs_CRP and correlative to other sleep disorders. In fully-adjusted linear regression model, poor sleep quality was significantly associated with elevated hs_CRP (log transformed) among the overall sample and in females only (beta = 0.10, se = 0.03, p<0.01 and beta = 0.13, se = 0.04, p<0.01, respectively). In fully-adjusted logistics regression model, poor sleep quality was linked with risk of high CRP(OR: 1.42, 95% CI: 1.15-1.76 in overall sample and OR: 1.59, 95%CI: 1.18-2.14 in females, respectively). Conclusion: We found that poor sleep quality was independently associated with elevated hs_CRP in females but not in males in a U.S. adult population.