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Purpose: To investigate structural brain changes and their relationship with cognitive function by determining the alterations of white matter integrity and changes in hippocampal volume that occur during chronic obstructive pulmonary disease (COPD). Materials and Methods: Diffusion tensor images and 3D-T1 MR images were acquired in 13 male nonhypoxemic COPD patients and 13 age- and gender-matched healthy controls. Global probabilistic tractography was used to assess a total of 18 major tracts. We examined the association between the hippocampal volume and diffusivity parameters of white matter tracts. Results: A significant difference in diffusion parameters between groups was identified for 11 white matter bundles (p < 0.05). No association was demonstrated between the normalized hippocampus volume and diffusion parameters among the participants. Significant associations between Korean version of the Mini-Mental State Examination (KMMSE) scores and diffusivities were found for six tracts (p < 0.05). Of note, the mean diffusivity (MD) and redial diffusivity (RD) of the left superior longitudinal fasciculus parietal segment showed a significant negative correlation with the K-MMSE score (MD: r = -0.623, p = 0.001; RD: r = -0.408, p = 0.048). Conclusion: Altered white matter integrity was demonstrated across regional white matter bundles, including the superior longitudinal fasciculus, in COPD patients, and it was related to cognitive function. Changes in the volume of the hippocampus should be investigated in further studies. [ABSTRACT FROM AUTHOR]