Chronic Obstructive Pulmonary Disease (COPD) coexists with co-morbidities. While co-morbidity has been associated with poorer health status, it is unclear which conditions have the greatest impact on self-rated health. We sought to determine which, and how much, specific co-morbid conditions impact on self-rated health in current and former smokers with self-reported COPD. Using the 2001-2008 National Health and Nutrition Examination Survey we characterized the association between thirteen co-morbidities and health status among individuals self-reporting COPD. Adjusted odds ratios (ORs) were generated using ordinal logistic regression. Additionally we evaluated the impact of increasing number of co-morbidities with self-rated health. Eight illnesses had significant associations with worse self-rated health, however after mutually adjusting for these conditions, congestive heart failure (OR 3.07, 95% CI 1.69-5.58), arthritis (OR 1.69, 95% CI 1.13-2.52), diabetes (OR 1.63, 95% CI 1.01-2.64), and incontinence/prostate disease (OR 1.63, 95% CI 1.01-2.62) remained independent predictors of self-rated health. Each increase in co-morbidities was associated with a 43% higher chance of worse self-rated health (95% CI 1.27-1.62). Individuals with COPD have a substantial burden of co-morbidity, which is associated with worse self-rated health. CHF, arthritis, diabetes and incontinence/prostate disease have the most impact on self-rated health. Targeting these co-morbidities in COPD may result in improved self-rated health.