Background Lower respiratory infections (LRI) are a major cause of mortality in China, yet there is a striking lack of nationally representative studies and comprehensive evaluations of their long-term economic impact. This study aimed to quantify the long-term economic burden of LRI across China''s 31 provinces and regions, and to assess the spatial distribution. Methods We used an improved health-augmented macroeconomic model (HMM) to estimate the economic burden of LRI in mainland China from 2020 to 2040. The model captures the burden via two channels: (1) the impact of LRI-related mortality and morbidity on labor supply, and (2) the effect of treatment costs on physical capital accumulation. Data were sourced from the China Provincial Burden of Disease Study 2023, the Global Burden of Antimicrobial Resistance Study, and other publicly available literature. Findings From 2020 to 2040, LRI are projected to impose a cumulative economic loss of CNY 363 billion (95% UI: 216-710). Marked regional disparities were observed: Guangdong incurred the highest absolute burden (CNY 35.6 billion); Guizhou reported the largest economic losses relative to 61 parts per thousand GDP; and per capita losses were greatest in Southwest China. Although East and Southwest China bore the largest overall losses, the disease burden was disproportionately concentrated in Southwest China, which accounted for 33.6% of DALYs but only 23.2% of the total economic loss. Middle-income regions experienced the highest total losses (CNY 174 billion), while per capita losses were most pronounced in low-income areas (CNY 426). Notably, the share of treatment-related costs increased with decreasing income levels, ranging from 21% in Northwest China to just 2% in East China. Interpretation The economic burden of LRI in China is substantial and regionally inequitable, underscoring the substantial economic returns to targeted LRI prevention and control-particularly in under-resourced regions. Far from being a fiscal liability, such investments offer meaningful long-term economic returns and are essential to advancing health and economic equity nationwide.