Remarks ■ The recommendation was based on two RCTs of 1308 infants aged 0–6 days with fast breathing (≥ 60 breaths per minute) as their only clinical sign in rural and semi-urban PHC facilities in four countries: the Democratic Republic of the Congo, Kenya, Nigeria and Pakistan. ■ For the trial examining oral amoxicillin versus placebo, the GDG considered that there was a small improvement in critical outcomes in the oral amoxicillin arm, based on low-certainty evidence. ■ For the trial examining oral amoxicillin versus penicillin IM plus gentamicin IM, the GDG considered that there were similar effects on critical outcomes in both arms; however, the evidence was very low certainty as there was serious imprecision (for treatment failure, RR 0.99, 95% CI: 0.77 to 1.27), a serious risk of bias (protocol deviations unbalanced between arms) and only a single study reporting outcomes. ■ The GDG recognized the possible adverse effects of oral antibiotics on the microbiome and AMR in young infants aged 0–6 days but considered that the benefits of oral antibiotics outweighed the potential risks. ■ The GDG also recognized that there were limited data on dose and duration of oral amoxicillin antibiotic therapy. Based on the trials included in the evidence review, the GDG considered that the following antibiotic dose should be used: oral amoxicillin 50 mg/kg every 12 hours for at least 7 days. ■ The GDG made a strong recommendation despite the limited evidence in non-hospital settings as they felt strongly about the importance of providing clear guidance for the management of unwell infants when referral to hospital is not possible. The GDG were able to use their knowledge and experience in best practice clinical management of fast breathing in young infants to make this recommendation by consensus.