Systemic Lupus Erythematosus (SLE) is a common disease with extremely heterogeneous neurological manifestations in its clinical expression. However, few cases have been reported in the last 50 years when the initial manifestation of SLE is Guillain-Barré syndrome (GBS). Our work highlights the importance of evoking SLE as a potential etiology in a patient presenting with acute polyradiculoneuritis. We report the case of a 41-year-old woman who presented with dyspnoea with a purely proxo-distal motor deficit in all four limbs with dermatological lesions such as generalized myxedema and alopecia. The clinical electrical and biological presentation confirms acute polyradiculoneuritis revealing systemic lupus erythematosus. The outcome was marked by clinical improvement, despite the severity of the clinical picture, after treatment with corticosteroid and cyclophosphamide boluses. In conclusion, neurological manifestations in lupus disease are common, whereas the form of acute polyradiculoneuropathy is very rare with a committed vital prognosis. Early diagnosis and management are essential.