BACKGROUND AND OBJECTIVES Seasonal influenza vaccination has been shown to reduce the risk of influenza and severe complications among children 6 months and older. Since 2010, reported numbers of influenza-associated pediatric deaths among children aged <18 years have ranged from 37 during the 2011–2012 season to 289 during 2024–2025. We estimated influenza vaccine effectiveness (VE) against pediatric death from 2016–2017 through 2024–2025.

METHODS We conducted a case-cohort analysis comparing current season influenza vaccination status among reported influenza-associated pediatric deaths with survey estimates of influenza vaccination coverage in pediatric age groups. Underlying medical conditions and current seasonal influenza vaccination were obtained from surveillance case reports. We estimated vaccination odds ratios (OR) and 95% confidence intervals (CI) from logistic regression comparing influenza vaccination among children who died with vaccination coverage in comparison cohorts. VE was calculated as (1 – OR) × 100.

RESULTS From August 2016 through July 2025, 1234 laboratory-confirmed influenza-associated pediatric deaths were reported among children aged 6 months--17 years. Of 1086 reported deaths including influenza vaccination information, 124 (23%) of 530 children with underlying medical conditions and 70 (13%) of 556 children without known conditions were fully vaccinated against influenza. Average influenza vaccination coverage in survey cohorts was 49%. VE was 80% (95% CI, 75% to 84%) overall, 77% (95% CI, 71% to 82%) among children with underlying medical conditions and 87% (95% CI, 84% to 89%) among children without known conditions.

CONCLUSIONS Influenza vaccination reduced risk of fatal influenza among children with or without known underlying medical conditions.