Background: Due to limited existing data, we investigated health-related quality of life HrQoL in Filipino persons undergoing TB treatment, and if it is negatively impacted by co-morbidity with undernutrition, diabetes and anaemia. Methods: Adult participants were enrolled in public facilities in Metro Manila (3 sites) and Negros Occidental (2 sites). Multivariate linear regression was used to model the four correlated domain scores from the WHOQOL-BREF questionnaire (physical, psychological, social, environmental). A forward-stepwise approach was used to select a final multivariable model with inclusion based on global tests of significance with p<0.1. Results: In 446 persons on drug-sensitive TB treatment, diabetes and moderate/severe anaemia were not associated with HrQoL. After adjustment for age, sex, education, food insecurity, treatment adherence, inflammation, category I or II TB treatment, treatment phase, current side effects and inhibited ability to work, moderate/severe undernutrition (BMI<17 kg/m2) was associated with lower HrQoL (p=0.003) with reduced psychological (coefficient:-1.02; 95% CI: -1.54, -0.51), physical (-0.62; -1.14, -0.09) and environmental domain scores (-0.45; -0.88,-0.01). In 225 patients with known HIV status in Metro Manila, HIV was associated with modestly reduced HrQoL (p=0.014). Conclusions: Nutritional status and food insecurity represent modifiable risk factors for poor HrQoL that may be alleviated through interventions.