PURPOSE: This study assessed the effects of TB stigma and social support on the health-related quality of life (HRQoL) of people living with drug-resistant tuberculosis (DR-TB) in Lagos, Nigeria. METHODS: A cross-sectional study was conducted in five DR-TB treatment centres in Lagos, Nigeria, between September and December 2023. A total of 203 adults on DR-TB treatment were recruited to complete a questionnaire including the Redwood DR-TB stigma scale, the Functional Assessment of Chronic Illness Therapy-TB (FACCIT) scale, and the Multidimensional Scale of Perceived Social Support (MSPSS). Student 't' test/one-way ANOVA, Pearson's correlation, and hierarchical linear regression analysis were conducted to explore the factors associated with HRQoL and the relationships between stigma, social support, and HRQoL. RESULTS: The mean overall HRQoL was 41.1 ± 12.9 among people with DR-TB. The HRQoL score of the physical domain was the lowest (25.8 ± 13.8). Participants who were young, male, single, with higher education, and HIV-negative had higher HRQoL than their counterparts (p <
0.05). Stigma was negatively associated with HRQoL, while social support was positively related, collectively explaining 57.6% of the variance. In the final model, social support contributed more (B = 0.576) to predicting HRQoL than did stigma (B = - 0.414). CONCLUSION: The overall HRQoL of people with DR-TB in Lagos, Nigeria, was poor. Strategies that improve social support systems and reduce stigma are needed to improve this. Further studies are also required to assess the changes in HRQoL over time and evaluate the impact of specific stigma-reduction interventions.