Objective As the proportion of children living low malaria transmission areas in sub-Saharan Africa increases, approaches for identifying non-malarial severe illness need to be evaluated to improve child outcomes.

Design As a prospective cohort study, we identified febrile paediatric inpatients, recorded data using Integrated Management of Childhood Illness (IMCI) criteria, and collected diagnostic specimens.

Setting Tertiary referral centre, northern Tanzania.

Results Of 466 participants with known outcome, median age was 1.4 years (range 2 months–13.0 years), 200 (42.9%) were female, 11 (2.4%) had malaria and 34 (7.3%) died. Inpatient death was associated with: Capillary refill >3 s (OR 9.0, 95% CI 3.0 to 26.7), inability to breastfeed or drink (OR 8.9, 95% CI 4.0 to 19.6), stiff neck (OR 7.0, 95% CI 2.8 to 17.6), lethargy (OR 5.2, 95% CI 2.5 to 10.6), skin pinch >2 s (OR 4.8, 95% CI 1.9 to 12.3), respiratory difficulty (OR 4.0, 95% CI 1.9 to 8.2), generalised lymphadenopathy (OR 3.6, 95% CI 1.6 to 8.3) and oral candidiasis (OR 3.4, 95% CI 1.4 to 8.3). BCS <5 (OR 27.2, p<0.001) and severe wasting (OR 6.9, p<0.001) were independently associated with inpatient death.

Conclusions In a low malaria transmission setting, IMCI criteria performed well for predicting inpatient death from non-malarial illness. Laboratory results were not as useful in predicting death, underscoring the importance of clinical examination in assessing prognosis. Healthcare workers should consider local malaria epidemiology as malaria over-diagnosis in children may delay potentially life-saving interventions in areas where malaria is uncommon.