The changing climate is one of the most important factors affecting public health. Older people are particularly threatened due to their less efficient immune systems. To evaluate the potential benefits of short-term indoor dehumidification on their circulation and cardiopulmonary health, we conducted a random, cross-over experiment with 36 healthy residents of an aged-care center in Chongqing, China in 2020. Vapor compression dehumidifiers were used over two 48-h periods. At the end of each 48 h, we immediately measured sixteen circulatory system biomarkers of inflammation, coagulation, and oxidative stress; lung function; blood pressure; and heart rate. Indoor temperature and relative humidity were monitored throughout the study period. Linear, mixed-effect models were used to associate health endpoints with indoor relative humidity. This intervention study showed that when the indoor relative humidity decreased from 75% to 45%: (1) the coagulation indicators, sCD40l, and PAI-1, decreased significantly, by 58.82% and 23.50%, respectively; (2) the inflammatory indicators, CRP, IL-6, and TNF-α decreased significantly, by 4.09%, 25.78%, and 10.60%, respectively; (3) PEF, FEV1 and FVC were increased significantly by 20.08%, 14.54%, and 15.75% respectively. To the best of our knowledge, this is the first study to examine the impact of short-term dehumidification on clinical and biochemical measures of cardiorespiratory health in humid areas, and our study suggests that RH in the dehumidified rooms (46.9 ± 8.7%) may be healthier than that in humid rooms (75.2 ± 7.9%). Humidity may be involved in the development of atherosclerosis by activating oxidative stress and mediating the secretion of inflammatory indicators. At the same time, platelet activation induced by oxidative stress stimulates thrombosis to increase cardiovascular risk in older people. Conclusion: This intervention study shows that in a Chinese city like Chongqing with serious indoor environmental humidity, indoor short-term dehumidification has obvious cardiopulmonary benefits for the healthy elderly. Display omitted •This is the first study to explore the cardiopulmonary health effects of indoor relative humidity by a randomized cross-trial.•Air dehumidification led to a significant decrease in inflammatory, coagulation and oxidative stress indicators.•Air dehumidification led to a significant increase in lung function indicators.•Indoor short-term dehumidification has obvious cardiopulmonary benefits for the healthy elderly.