OBJECTIVE The authors aimed to understand the alterations of brain resting-state networks (RSNs) in patients with pan-brachial plexus injury (BPI) before and after surgery, which might provide insight into cortical plasticity after peripheral nerve injury and regeneration. METHODS Thirty-five patients with left pan-BPI before surgery, 30 patients after surgery, and 25 healthy controls underwent resting-state functional MRI (rs-fMRI). The 30 postoperative patients were subdivided into 2 groups: 14 patients with improvement in muscle power and 16 patients with no improvement in muscle power after surgery. RSNs were extracted using independent component analysis to evaluate connectivity at a significance level of p < 0.05 (familywise error corrected). RESULTS The patients with BPI had lower connectivity in their sensorimotor network (SMN) and salience network (SN) and greater connectivity in their default mode network (DMN) before surgery than the controls. Connectivity of the left supplementary motor cortex in the SMN and medial frontal gyrus and in the anterior cingulate cortex in the SN increased in patients whose muscle power had improved after surgery, whereas no significant changes were noted in the unimproved patients. There was a trend toward reduction in DMN connectivity in all the patients after surgery compared with that in the preoperative patients; however, this result was not statistically significant. CONCLUSIONS The results of this study highlight the fact that peripheral nerve injury, its management, and successful treatment cause dynamic changes within the brain's RSNs, which includes not only the obvious SMN but also the higher cognitive networks such as the SN and DMN, which indicates brain plasticity and compensatory mechanisms at work.