Background: Neuroimaging investigations have already uncovered alterations to cerebral microstructural integrity in patients with fibromyalgia (FM). In the meantime, these patients commonly suffer from depression and anxiety.Objective: In this study, microstructure changes within white matter were examined in patients with FM with consideration of concurrent physiological factors.Study Design: A cross-sectional case-control study.Setting: A university hospital.Methods: Diffusion tensor imaging was performed on 20 patients with FM and 20 healthy controls. The 4 diffusional indices, namely, fractional anisotropy (FA), mean, radial, and axial diffusivity (MD, RD, AD) were calculated using tract-based spatial statistics. The relationships between the diffusional parameters and pain scales were also examined.Results: The patients with FM exhibited enhanced FA, reduced MD, RD, and AD in numerous white matter tracts, including the corpus callosum, corona radiata, internal capsule, corticospinal tract, posterior thalamic radiation, cerebellar peduncle, sagittal stratum, and superior fronto-occipital fasciculus. When depression and anxiety were added as covariates, most between-group diffusional difference disappeared except for AD reduction in the corona radiate, internal capsule, and cerebellar peduncle (P < 0.05, threshold-free cluster enhancement corrected). The diffusion tensor imaging measures were not correlated with clinical variables.Limitation: A relatively small sample size.Conclusion: Our results demonstrate that disrupted white matter microstructure in patients with FM is mainly restricted to tracts associated with pain sensory processing and motor control, adjusting for psychosocial factors. A considerable degree of difference in white matter characteristics may be explained by the patients with FM group's greater level of psychological distress.