Abstract Body: Background: Evidence suggests participation in aerobic and muscular strengthening physical activity (PA) is associated with a decrease in risk for all-cause mortality. Elevated C-reactive protein (CRP), a marker of low-grade chronic inflammation, is associated with an increased risk for mortality. Few studies have examined whether PA mitigates the increased risk for mortality associated with elevated CRP. Purpose: Examine the association between self-reported PA and all-cause mortality among a representative sample of U.S. adults with elevated CRP. Methods: Data from the 1999-2006 National Health and Nutrition Examination Survey were used. Particpants were adults (40-79 years, mean age 55.6 years, n=2,635) with elevated CRP (3-10 mg/L) who participated in data collection from the Mobile Examination Center. Aerobic PA was categorized as meeting the guidelines (≥500 MET-minutes/week), some activity (>0-<500 MET-minutes/week), and no aerobic PA. Muscular strengthening activity (MSA) was categorized as meeting (≥2 days/week) or not meeting the guidelines (<2 days/week). All-cause mortality was the dependent variable. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) across the categories of aerobic PA and MSA. Results: In the total sample, those meeting the aerobic PA guidelines had a significant reduction in all-cause mortality (HR: 0.75, 95% CI: 0.61-0.92, p=0.007). When stratified by gender, similar findings were revealed found among men (HR: 0.72, 95% CI: 0.54-0.96, p=0.03) and women (HR 0.59, 95% CI 0.43-0.80, p=0.001). No risk reduction was found for MSA participation. Conclusions: Among U.S. adults with elevated CRP, meeting current aerobic PA guidelines significantly reduced the risk for all-cause mortality in both men and women. Future studies should examine effects of domain-specific PA, objectively measured (e.g., accelerometer-derived) PA, and/or more precise measures of MSA and all-cause mortality among those living with chronic systemic inflammation.