Clinical algorithms used in the assessment of febrile children in the Paediatric Emergency Departments are commonly based on threshold values for vital signs, which in children with fever are often outside the normal range. Our aim was to assess the diagnostic value of heart and respiratory rate for serious bacterial infection (SBI) in children after temperature lowering following administration of antipyretics. A prospective cohort of children presenting with fever between June 2014 and March 2015 at the Paediatric Emergency Department of a large teaching hospital in London, UK, was performed. Seven hundred forty children aged 1 month–16 years presenting with a fever and ≥ 1 warning signs of SBI given antipyretics were included. Tachycardia or tachypnoea were defined by different threshold values: (a) APLS threshold values, (b) age-specific and temperature-adjusted centiles charts and (c) relative difference in z-score. SBI was defined by a composite reference standard (cultures from a sterile site, microbiology and virology results, radiological abnormalities, expert panel). Persistent tachypnoea after body temperature lowering was an important predictor of SBI (OR 1.92, 95% CI 1.15, 3.30). This effect was only observed for pneumonia but not other SBIs. Threshold values for tachypnoea > 97th centile at repeat measurement achieved high specificity (0.95 (0.93, 0.96)) and positive likelihood ratios (LR + 3.25 (1.73, 6.11)) and may be useful for ruling in SBI, specifically pneumonia. Persistent tachycardia was not an independent predictor of SBI and had limited value as a diagnostic test.