We performed a prospective study in 32 patients with Guillain-Barre syndrome (GBS) or its variants to correlate intraepidermal nerve fiber density (IENFD) at the distal leg and lumbar region with pain, autonomic dysfunction, and outcome. In the acute phase, IENFD was reduced in 60% and 61.9% of patients at the distal leg and lumbar region, respectively. In the acute phase, 43.7% of patients complained of neuropathic pain. Their IENFD at the distal leg was significantly lower than in patients without pain (P < .001) and correlated with pain intensity (r(s) = -0.51; P = .003). Intriguingly, also patients with the pure motor variant of GBS and pain had low IENFD. At 6-month follow-up, only 3 patients complained of persisting neuropathic pain, whereas 3 patients reported late-onset pain symptoms. IENFD in the acute phase did not predict presence or intensity of pain at 6-month follow-up. IENFD in the acute phase did not correlate with clinical dysautonomia or GBS severity at nadir. However, it correlated with poorer GBS disability score at 6 months (P = .04), GBS score at nadir (P = .03), and clinically probable dysautonomia (P = .004). At 6-month follow-up, median IENFD remained significantly low both at the distal leg (P = .024) and lumbar region (P = .005). Double and triple staining confocal microscope studies showed diffuse damage of myelinated dermal nerves along with axonal degeneration, and mononuclear cell infiltration. Unmyelinated and myelinated skin nerves are diffusely affected in GBS and its variants, including the pure motor form. IENFD declines early, remains low over time, correlates with pain severity in the acute phase, and may predict long-term disability. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.