Immune reconstitution inflammatory syndrome (IRIS) in the setting of antiretroviral therapy is well described, but it is not as common in non-HIV patients; here, we present a case of immune reconstitution inflammatory syndrome presenting as acute respiratory distress syndrome in a leukemia patient who had neutropenic fever and septic shock after high-dose cytarabine. During neutropenia recovery, his chest X-ray showed progressive worsening despite being on adequate therapy, we started him on steroids which resulted in significant clinical improvement.