For patients with chronic lower respiratory disease, hypobaric hypoxia at a high altitude is considered a risk factor for mortality. However, the effects of residing at moderately high altitudes remain unclear. We investigated the association between moderate altitude and chronic lower respiratory disease mortality. In particular, we examined the lower 48 United States counties for age-adjusted chronic lower respiratory disease mortality rates, altitude, and socioeconomic factors, including tobacco use, per capita income, population density, sex ratio, unemployment, poverty, and education between 1979 and 1998. The socioeconomic factors were incorporated into the correlation analysis as potential covariates. Considerable positive (R = 0.235; P <0.001) and partial (R = 0.260; P <0.001) correlations were observed between altitude and chronic lower respiratory disease mortality rate. In the subgroup with high COPD prevalence subgroup, even stronger positive (R = 0.346; P <0.001) and partial (R = 0.423, P <0.001) correlations were observed. Multivariate regression analysis of all available socioeconomic factors revealed that additional knowledge on altitude improved the adjusted R2 values from 0.128 to 0.186 for all counties and from 0.301 to 0.421 for counties with high COPD prevalence. We concluded that in the lower 48 United States counties, even a moderate altitude may pose considerable risks in patients with chronic lower respiratory disease.