Background: Multidrug-resistant tuberculosis (MDR TB) affects the physical, psychosocial and inter-relationship structure and thus quality of life (QoL) of an individual. WHO QOL BREF is presumed to capture the QoL construct. This study investigates the diagnostic accuracy and construct of WHO QOL BREF from a psychometric perspective and complements and converges findings through classical test theory. Methods: The instrument validity study was conducted in a district of Central India amongst the microbiologically confirmed MDR TB cohort of year 2017 (n=98). We calculated global and domain-specific Cronbach alpha and Inter-domain Pearson correlations. The dichotomized items were fitted through Rasch model for item endorsement, response pattern and for variation inconsistencies. Item Characteristic Curves and person item maps were also plotted. We performed DIF (Differential Item Functioning) to check the effect of subgroups on underlying traits. This was complimented with an Exploratory Factor Analysis (EFA) using oblique ProMax rotation. The optimum number of factors were identified by Scree plot and parallel analysis approach and the emerging factor structure was compared with the result obtained through the Rasch model. Results: The global Cronbach’s alpha was 0.94 (95% CI 0.92-0.96). Social relationship domain had poor correlations with all three domains (r=0.42, r=0.41 r=0.58), higher beta values and less discrimination. DIF showed a differential response by gender. There was a visual clustering and a non-uniform distribution of items across the perceived QoL. A 3-factor model emerged through EFA and was reframed on the notion of self-concept. Items related to pain, medical aid had significant misfit and weak factor loading while items of sexual activity and social support had relatively poor performance in Infit, Wald, DIF on factor loading parameters. Conclusions: The study indicates the possible deviation of scale from theorized dimensional construct in Indian MDR TB context more with the items of the social relationship domain.