Abstract Background: Chronic inflammation is associated with adverse lifestyle factors, including poor diet, lack of physical activity and smoking. Systemic inflammation also plays an important role in carcinogenesis, and can be measured by C-reactive protein (CRP), an acute phase protein that is elevated in those with cancer. We recently examined associations of CRP and lifestyle factors with fatal lung cancer in the NHANES III cohort and reported significant associations, which varied by smoking status and gender. The purpose of this study was to examine associations between baseline lifestyle factors and CRP levels in this same cohort and to determine if differences existed by smoking status and gender. Methods: Data from cancer-free individuals >age 40 in the Third National Health and Nutrition Examination Survey (NHANESIII:1988-1994) were examined to assess relationships between exercise patterns, dietary factors (measured by the Healthy Eating Index (HEI)) and inflammation (CRP≥3 versus CRP<3). Baseline demographic and clinical data were obtained from interviews and lab examinations. Logistic regression was performed to estimate odds ratios (ORs) for the entire cohort and by smoking status and gender. Results: Out of 8,950 participants who were eligible for this study, 52% were female, 73% were white, mean age was 61 years, and over half had ever smoked >100 cigarettes (55%). Significant inverse relationships were found in univariate models between elevated CRP and several types of physical activity performed in the past 30 days (walking, jogging, biking, swimming, gardening, lifting weights; p<0.0001), with the lowest OR = 0.43 for walking. In multivariate models stratified by gender and smoking status, the OR for walking increased to 0.78 but remained statistically significant for all but non-smokers (p<0.01). Significant inverse relationships with CRP were also observed for serum selenium (OR = 0.50), serum vitamin D (OR = 0.85) and HEI score (OR = 0.94) in univariate models (p<0.0001). When stratified in multivariate models, however, the OR estimates for selenium remained similar and statistically significant in all groups (p<0.05), but the ORs for serum vitamin D and HEI score were only significant for smokers and males [OR = 0.90 (p<0.01) and OR = 0.92 (p = 0.001), respectively]. Discussion: This analysis showed that healthier diet and increased physical activity were associated with decreased levels of CRP, especially for smokers and males, which few studies have examined. These results are in line with those of our prospective study, which showed reductions in lung cancer deaths from increased physical activity and healthier eating, primarily in smokers and males. Since male smokers comprise the highest risk group for lung cancer, these findings are very important in the context of lung cancer prevention, especially regarding the potential role of inflammation. Future studies should further assess reasons for differences among these subgroups.. Citation Format: Marisa A. Bittoni, Steven K. Clinton, Randall E. Harris, Brian Focht. Associations between exercise, diet and inflammation: Results from NHANES III. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1753.