Abstract Background To estimate crude mortality, excess mortality, and standardized mortality rates (SMR) among people living with HIV (PLHIV) initiating highly active antiretroviral therapy (HAART) in Luzhou, China 2006–2020, and assess associated factors. Methods PLHIV initiating HAART in the HIV/AIDS Comprehensive Response Information Management System (CRIMS) in Luzhou, China 2006–2020 were included in the retrospective cohort study. The crude mortality, excess mortality, and SMR were estimated. Multivariable Poisson regression model was used for analyzing risk factors associated with excess mortality rates. Results The median age among 11,468 PLHIV initiating HAART was 54.5 years (IQR:43.1–65.2). The excess mortality rate decreased from 1.8 deaths/100 person-years (95% confidence interval [CI]:1.4–2.4) in 2006–2011 to 0.8 deaths/100 person-years (95%CI:0.7–0.9) in 2016–2020. SMR decreased from 5.4 deaths/100 person-years (95%CI:4.3–6.8) to 1.7 deaths/100 person-years (95%CI:1.5–1.8). Males had greater excess mortality with the eHR of 1.6 (95%CI:1.2–2.1) than females. PLHIV with CD4 counts ≥ 500 cells/μL had the eHR of 0.3 (95%CI:0.2–0.5) in comparison to those with CD4 counts