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This chapter discusses the diagnosis, evaluation and management of neutropenic fever. The initial presentation of the critically ill with neutropenic fever may be overt with a clinical presentation similar to that of septic shock and including hypotension, respiratory failure, or any other major organ dysfunction. It may also be cryptogenic with isolated confusion, coagulopathy, or cardiac arrhythmias. Elderly patients and those taking steroids may present as hypothermic or euthermic. Any unexplained acute clinical deterioration should be considered a fever equivalent. Critically ill patients with neutropenic fever will most frequently present with common infections. However, their immunocompromised state places them at risk for more complex disease processes of almost any organ system. The pathophysiology of the decompensating patient with neutropenic fever is similar to that of a patient in septic shock. Those patients should be resuscitated similarly by the rapid and aggressive administration of crystalloids.