Background: Quadriplegic myopathy (QM) and its variants generally are described in critically ill patients who are exposed to steroids and nondepolarizing muscle blocking agents (NDMBAs). Methods: A patient with sepsis who was not exposed to steroids or an NDMBA infusion developed QM and was studied using serial quantitative electromyography. Results: Clinical and electrophysiological studies identified evidence of a severe myopathy and muscle biopsy showed necrosis, calcifications and selective loss of myosin filaments in non-necrotic fibers. Her clinical recovery paralleled rises in motor unit action potential (MUAP) amplitudes studied by serial automatic decomposition electromyography (ADEMG). Conclusions: QM can develop with sepsis and without significant exposure to steroids and NDMBAs. ADEMG can be a useful tool in electrophysiological evaluation of critically ill patients with weakness.