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Background: We aimed to determine the trend of TB-related deaths during the COVID-19 pandemic., Methods: TB-related mortality data of decedents aged ≥25 years from 2006 to 2021 were analyzed. Excess deaths were estimated by determining the difference between observed and projected mortality rates during the pandemic., Results: A total of 18,628 TB-related deaths were documented from 2006 to 2021. TB-related age-standardized mortality rates (ASMRs) were 0.51 in 2020 and 0.52 in 2021, corresponding to an excess mortality of 10.22 and 9.19%, respectively. Female patients with TB demonstrated a higher relative increase in mortality (26.33 vs. 2.17% in 2020; 21.48 vs. 3.23% in 2021) when compared to male. Female aged 45-64 years old showed a surge in mortality, with an annual percent change (APC) of -2.2% pre-pandemic to 22.8% (95% CI: -1.7 to 68.7%) during the pandemic, corresponding to excess mortalities of 62.165 and 99.16% in 2020 and 2021, respectively; these excess mortality rates were higher than those observed in the overall female population ages 45-64 years in 2020 (17.53%) and 2021 (33.79%)., Conclusion: The steady decline in TB-related mortality in the United States has been reversed by COVID-19. Female with TB were disproportionately affected by the pandemic., Competing Interests: FJ: Speaker: Gilead Sciences, MSD, and Ascletis. Consulting/advisory board: Gilead and MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Deng, Liu, Lv, Li, Qi, Bo, Qiu, He, Ji, Zeng and Gao.)