Spatial integration of parts of the body is impaired in patients with complex regional pain syndrome (CRPS). Since the training of mental rotation (MR) has been shown to be among the effective therapy strategies for CRPS, impairment of MR is also important for the pathophysiological understanding of CRPS. The aim of this study was to evaluate whether differences in neural representation of MR occur between CRPS patients and healthy controls. Therefore we included 15 chronic CRPS patients and 15 age-/gender matched healthy controls. We assessed behavioral (accuracy and reaction time for MR of both hands), clinical (DASH) and MRI (T1, fMRI during MR) data. Reaction times in the patient group were delayed compared to healthy controls without a lateralization effect for affected hand side. Although both groups showed an activation pattern typical for MR, only HC showed a highly significant contrast for the rotated versus unrotated hands in the right intraparietal sulcus. CRPS patients showed a reduction of fMRI activation in areas including subthalamic nucleus, nucleus accumbens and putamen. Regression analysis for the CRPS group emphasized the importance of putamen and n. accumbens activation for MR performance. This study highlights the reduced access of CRPS patients for mental resources modulating arousal, emotional response and subcortical sensorimotor integration. PERSPECTIVE: This study localized the underlying neural responses for impaired mental rotation (MR) in patients with complex regional pain syndrome (CRPS) as a decrease in basal ganglia (putamen) and nucleus accumbens activation.