Objective To estimate the contribution of infections to childhood deaths in England and Wales over a 3-year period.

Design Retrospective analysis of national electronic death registration data.

Setting England and Wales.

Patients Children aged 28 days to 15 years who died during 2013–15.

Main outcome measures The proportion of children who died of infection compared with total deaths over 3 years; the main pathogens responsible for infection-related deaths in different age groups; comparison with similar data from 2003 to 2005.

Results There were 5088 death registrations recorded in children aged 28 days to <15 years in England and Wales during the three calendar years, 2013–2015 (17.6 deaths/100 000 children annually) compared with 6897 (23.9/100 000) during 2003–05 (incidence rate ratios (IRR) 0.74, 95% CI 0.71 to 0.77). During 2013–15, there were 951 (18.7%, 951/5088) infection-related deaths compared with 1368 (19.8%, 1368/6897) during 2003–05, equivalent to an infection-related mortality rate of 3.3/100 000 compared with 4.8/100 000 during the two periods (IRR 0.69, 95% CI 0.64 to 0.75), respectively. An underlying comorbidity was recorded in 55.0% (523/951) of death registrations during 2013–15 and increased with age. Where recorded, respiratory tract infection was the most commonly reported presentation (374/876, 42.7%) during 2013–15. Central nervous system infections accounted for only 4.8% (42/876). Overall, 63.1% (378/599) of infection-related deaths were associated with a bacterial, 34.2% (205/599) with a viral and 2.5% (15/599) with a fungal infection.

Conclusions Beyond the neonatal period, all-cause and infection-related childhood mortality rates have declined by 26% and 31%, respectively, over the past decade. However, infection continues to contribute to one in five childhood deaths.