Combined central and peripheral demyelination (CCPD) is a rare disease entity. Onset with the simultaneous central nervous system (CNS) and peripheral nervous system (PNS) involvement and its recurrence are exceptional. Anti-neurofascin antibodies have been shown to be present in up to 70% of cases, yet seronegative patients also exist. We present a case of seronegative recurrent CCPD. The PNS involvement was compatible with two episodes of recurrent Guillain-Barre syndrome (GBS), whereas the CNS involvement pattern was not typical for either multiple sclerosis (MS) or acute disseminated encephalomyelitis. The prognosis was excellent with pulse methylprednisolone, intravenous immunoglobulin, and plasmapheresis. This case highlights the varied clinical presentations of CCPD, extending beyond the realms of MS and chronic inflammatory demyelinating polyneuropathy, and underscores the potential for relapse. Importantly, to the best of our knowledge, this represents the inaugural instance of CCPD featuring PNS involvement in the form of recurrent GBS.