© 2018 Pavela et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Obesity and loneliness are associated with C-reactive protein (CRP), a predictor of cardiovascular disease. It is unknown whether the co-presence of obesity and loneliness is associated with additional risk for clinically elevated CRP. The present study thus examines their independent and combined effects on elevated CRP in older adults. Data come from 10,912 respondents who completed the 2008 and 2010 waves of the Health and Retirement Study. Loneliness was measured using an 11-item Loneliness Scale and body mass index was calculated from technician measured height and weight. Our primary outcome is high sensitivity CRP (hsCRP). Survey-weighted logistic regression models were used to test whether loneliness and BMI category are independent predictors of CRP after adjusting for demographics and other inflammatory-related covariates. In the fully adjusted model for men, obesity (OR = 2.36, p < .0001) was associated with increased odds of hsCRP >3.0. Among females, being overweight (OR = 1.75, p < .0001) or obese (OR = 4.01, p < .0001) were associated increased odds of hsCRP>3.0. Among both men and women, results from fully adjusted models indicated that loneliness was not associated with clinically elevated hsCRP (OR = 1.34, p = .0535; OR = 0.97, p = 0.6776, respectively).