OBJECTIVES: As the incidence of obesity continues to rise, there is pressure to find and evaluate new weight loss interventions; understanding the impact of obesity and weight loss on patients is an invaluable part of this process. We aimed to examine associations among patient characteristics, self-reported depression, vitality and the obesity and weight-loss quality-of-life (OWL-QOL) instruments in a population of overweight and obese patients. METHODS: We analysed baseline data from a clinical trial involving patients with body mass index (BMI) between 27–45kg/m2. Data included: patient demographics; obesity measures including BMI, weight and body composition; responses to the OWL-QOL questionnaire; responses to the Patient Health Questionnaire (PHQ), assessing depression; and responses to the SF-36 vitality subscale. Least angle regression (LAR) was used to select the most relevant obesity measures to include in multivariable regression models. Univariate associations were examined using Spearman’s correlations. RESULTS: Baseline data were available for 341 patients with a mean age of 44.2 (SD=10.7) years, mean BMI of 35.2 (SD=4.67) kg/m2, and mean OWL-QOL total score of 55.3 (SD=24.2). 83.3% were female. LAR showed that among obesity measures, percentage of total fat was most significantly associated with the OWL-QOL total score. Based on Spearman’s correlations, the OWL-QOL total score was significantly correlated with gender (ρ=0.233, p<0.001), total fat (ρ=-0.264, p<0.001), PHQ (ρ=-0.138, p=0.035), and vitality (ρ=0.456, p<0.001). In the final model (R2=0.34), vitality (β=0.55, p<0.001), female gender (β=-8.71, p=0.026) and race/ethnicity (β=12.3, African American versus Other, β=1.08 White versus Other; p=0.002 for both comparisons), but not percentage of total fat, were significantly associated with the OWL-QOL total score. CONCLUSIONS: The OWL-QOL was significantly associated with gender, race/ethnicity and vitality. Importantly, based on LAR, percentage of total fat was more significantly associated with the OWL-QOL total score than other obesity measures, including BMI.