not-yet-known not-yet-known not-yet-known unknown Background: Pediatric immunocompromised patients are at an increased risk of severe respiratory syncytial virus (RSV) infection. Here, we aimed to describe the clinical course and outcomes of RSV infection in immunocompromised children. Methods: This single-center study was conducted at St. Jude Children’s Research Hospital in immunocompromised children ≤21 years old, who had a positive RSV clinical test in the clinic or hospital from 2007 to 2019. Demographic and clinical characteristics, laboratory values, delays in the treatment of patients’ underlying conditions, and outcomes were extracted from the patients’ electronic medical records. Multivariate models were constructed to identify risk factors predictive of severe RSV LRTI. Results: In total, 391 patients were included. Most children (86%) were > 2 years of age, with a median age of 5 years. Acute lymphoblastic leukemia (ALL) was the most common underlying disease. Most patients presented with upper respiratory tract infections (n = 335; 85.7%). Approximately 6% of patients progressed to lower respiratory tract infections. More than half (58.8%) of the patients were hospitalized, and therapy for the underlying disease was modified or delayed due to RSV infection in one-third of the patients. Severe RSV infections were observed in 62 patients (15.9%). All-cause mortality was reported in 10 patients (2.6%), with three RSV-related deaths (0.7%). Conclusions: A high proportion of immunocompromised children with RSV infection require hospitalization. Hospitalization was observed in those aged >2 years, and an overall treatment delay for the underlying disease occurred in one-third of the patients. The burden associated with RSV in immunocompromised children is high irrespective of age and has direct and indirect consequences on their cancer treatment plans.