Guillain-Barré syndrome is the most common cause of acute neuromuscular paralysis in the western world. Subtypes of Guillain-Barré can cause both demyelinating and axonal damage to peripheral nerves, however skeletal muscle is not thought to be directly affected. We report the case of a 43 year-old male who presented with subacute progressive symmetrical limb weakness and sensory loss. Clinical examination, CSF assessment and neurophysiological testing were consistent with a diagnosis of Guillain-Barré syndrome. Serology confirmed recent Campylobacter infection. Following admission the patient developed severe aching pain in his thighs, treated initially with tramadol and amitriptyline, and also displayed signs of significant autonomic instability. Over a 20-day period his serum CK progressively increased, to a peak of 17,423 IU/L, with associated severe renal impairment. Following this peak, the CK gradually improved back to normal. This is the largest rise in CK ever reported in Guillain-Barré syndrome, and has a number of possible explanations. Release of muscular CK in GBS could be a result of rapid extensive denervation due to axonal degeneration of motor terminals, thus causing hyperexcitability in regional muscles. Alternatively, and given the associated autonomic changes, there may have been a co-existing neuroleptic malignant syndrome, or an iatrogenic serotonin syndrome.