Objectives: This study compared health-related quality of life (HRQoL) and depression among individuals with type 2 diabetes mellitus (T2D) and those at low or high risk for T2D. Methods: Respondents in a population-based US 2004 survey reported whether they had T2D (n = 3530) or risk factors for T2D [abdominal obesity, body mass index (BMI) >= 28 kg/m(2), dyslipidaemia, hypertension and history of cardiovascular disease]. Respondents without T2D were stratified into low risk (0-2 risk factors, n = 5335) and high risk (3-5 risk factors, n = 5051). SF-12 version 2 (SF-12) and Patient Health Questionnaire (PHQ)-9 were used to measure HRQoL and depression. Mean scores were compared across the three groups using analysis of variance. Linear regression identified factors associated with SF-12 Physical and Mental Component Summary scores (PCS and MCS), adjusting for age, gender, race, income, geographic region, household size, BMI and group. Results: Respondents were mostly women (60%) with mean age of 54 years. Mean PCS scores for T2D and high risk (39.5 and 41.7, respectively) were significantly lower than for low risk (50.6, p < 0.001). After adjustment, high-risk and T2D groups were associated with lower PCS and MCS scores compared with low risk group (p < 0.05). Mean PHQ-9 scores and per cent with moderate-to-severe depression were significantly higher for T2D and high risk than for low risk (p < 0.01). Conclusions: Health-related quality of life and depression scores in T2D were similar to those at high risk, and indicated significant decrements in physical health and greater depression compared with low-risk respondents.