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There has been tremendous growth in patients requiring critical care with severe infections. During a prolonged stay in the intensive care unit (ICU), patients develop critical illness polyneuropathy (CIP). The early identification of neurological involvement requires special attention during ICU care. We describe two cases who developed complete motor weakness after a prolonged stay in ICU. Patients were successfully managed with pyridostigmine and testosterone hormonal therapy initially and later with pyridostigmine only. The present case series highlights the need for early recognition, assessment, and novel management of CIP in ICU patients. However, the role of nutrition, physiotherapy, and supportive care is equally essential for the successful outcome in these patients.