Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in young children globally. We evaluated direct medical costs, caregiver work loss, and child quality of life (QoL) impairment associated with RSV hospitalization. Children ≤ 2 years with laboratory-confirmed RSV infection were prospectively identified between October 2020 and May 2023 at ten hospitals in Germany, Spain, Italy, France, and England. Direct costs were calculated based on country-specific unit costs per hospital day. Productivity loss and QoL impairment were ascertained by two validated, caregiver-administered instruments: 1) Work Productivity and Activity Impairment Questionnaire: Child's Hospitalization for Respiratory Illness (WPAI:CHRI), administered before discharge and 2) TNO AZL Child Quality of Life (TAPQOL), administered at baseline (shortly after admission) and before discharge. Among 382 hospitalized children, 261 (69%) were < 6 months and 306 (80%) were previously healthy. Median length of stay was 6 days (Interquartile Range (IQR) 4-8) and 50 (13%) were admitted to Paediatric Intensive Care Unit (PICU). Median hospital costs/admission were €4,266 (IQR 2,438-8,442), substantially varying by country (range €2,377-€8,541). Productivity loss was substantial with 129/211 (61%) employed caregivers reporting lost work-hours (mean 30.5 ± 18/admission). Child QoL was significantly reduced during RSV hospitalization in most domains, with the highest QoL impairment observed in the lung domain (mean difference 34.2 out of 100 [95% CI 30-38.4]. Conclusion: RSV hospitalization in children ≤ 2 years was associated with significant costs and QoL impairment in five European countries, emphasizing the importance of preventing severe RSV disease.