In one prospective cohort study, a diagnosis of asthma was associated with an increased risk of mortality in individuals with sickle cell anemia or HbSS. However, a direct relationship between death and asthma exacerbation could not be documented. This report examines two adolescents with sickle cell disease (SCD) who died during worsening symptoms consistent with asthma. Autopsies in both individuals demonstrated pulmonary airway smooth muscle hyperplasia, basement membrane thickening, and eosinophilia, consistent with bronchial asthma. Individuals with SCD and asthma warrant ongoing education, treatment, and surveillance for life-threatening complications of asthma. Pediatr Blood Cancer 2011;56:454–457. © 2010 Wiley-Liss, Inc.