BackgroundTB stigma represents a growing threat to TB care. Understanding TB stigma distribution and associating factors is crucial for effective TB control in Afghanistan. ObjectivesTo profile the prevalence of TB-related stigma and its associating factors among TB patients in Southern Afghanistan. MethodsIn this multi-center cross-sectional study, we randomly recruited 603 adult TB patients from 2 major TB treatment sites in Southern Afghanistan. A score of >8 on the Stigma Scale for Chronic Illness-8 items (SSCI-8 items) was considered as positive for TB-related stigma. We fitted a binary logistic regression model. ResultsOut of the 603 TB patients included in this study, 88.3% (95%CI: 85.8–90.9%) had TB-related stigma using the SSCI-8 cutoff (>8). Being in the age group 18–40 years, rural residence, no formal education, severe perception of illness, lack of TB knowledge, and symptoms of depression had positive associations with TB stigma. ConclusionA considerable percentage (88.3%) of patients had TB stigma. We identified potential risk factors that could serve as a benchmark for guiding policy efforts and interventions that aim to reduce stigma among TB patients in Afghanistan.