OBJECTIVES: To evaluate the effect of symptoms of diabetic peripheral neuropathy (SDPN), diabetic retinopathy (DR) and co-morbid SDPN & DR (COMORB) on the Healthy Days Core Module (HRQOL-4) measures of the CDC, among US adults =40 years old with diagnosed diabetes, using the 2001-2002 National Health and Nutrition Examination Survey (NHANES). METHODS: Logistic and ordinary least squares (OLS) regression models were used to assess the impact of SDPN, DR and COMORB on HRQOL-4 measures. Included in the analysis were 429 NHANES respondents =40 years old classified as having diagnosed diabetes. Model covariates included age, gender, race, education, current smoking status, currently asthmatic, and history of cardiovascular disease, cancer, arthritis, COPD, hypertension and stroke. The conditions of interest were assessed based upon respondent self-report. All estimates were generated using Stata statistical software, and accounted for the complex survey design of NHANES. RESULTS: Using the 2001-2002 NHANES, we estimated that, among US adults =40 years old with diagnosed diabetes, those with SDPN (OR = 7.66; 95%CI = 2.90, 20.23), DR (3.43; 1.53, 7.69), and COMORB (5.43; 2.32, 12.73) were all more likely to report that they were currently in poor health, compared to those without the condition of interest. Additionally, OLS models suggest that those with SDPN had a significantly greater number of days during the past month in which their physical health was not good, compared to those without SDPN. SDPN was also associated with a significantly greater number of days during the past month in which poor physical or mental health limited usual activities. CONCLUSION: Among US adults =40 years old with diagnosed diabetes, SDPN, DR, and COMORB all appear to have a significant negative effect on quality-of-life. Future therapies that offer relief of these conditions may have considerable humanistic benefits.