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Immune-mediated necrotizing myopathy is a very rare inflammatory disease affecting skeletal muscles. Immune-mediated necrotizing myopathy may be associated with myositis-specific autoantibodies including anti–single recognition particle and anti–3-hydroxy-3- methylglutaryl-coenzyme A reductase, infectious agents (HIV or hepatitis C), other connective tissue disorders (such as scleroderma), and malignancy. We reported a 28-year-old healthy woman presented with subacute onset ascending muscle weakness 2 weeks after an annual influenza vaccination. Cerebral Spinal Fluid study showed normal cell counts with elevated protein and nerve conduction study showed reduced diffuse compound muscle action potential amplitudes suggesting a diagnosis of Guillain–Barré syndrome. Despite treatment using intravenous immunoglobulin, her condition continued to get worse with new bulbar and respiratory muscle weakness. Eventually, the diagnosis of anti–single recognition particle–mediated necrotizing myopathy was made based on elevated creatine kinase, thigh magnetic resonance imaging, muscle biopsy, and positive antibody testing. Our patient responded to the combination of intravenous immunoglobulin, prednisone, and anti-CD20 monoclonal antibody, rituximab.