Serious bacterial and viral infections occurring in early infancy are important factors affecting morbidity and mortality. Recognition of sepsis by healthcare professionals is vital and allows initiation of appropriate early treatment which can be life-saving and improve outcomes for these infants greatly. This article outlines the leading causes of sepsis, for example, group B Streptococcus (GBS), Escherichia coli and herpes simplex virus. We discuss the non-specific ways in which an infant with a serious infection may present to health professionals and highlight crucial features to look for in the history and during examination of an unwell infant, and these include ‘red-flag’ signs and symptoms that should be carefully elicited. A systematic approach for the management of an infant with suspected sepsis based on up-to-date evidence and the National Institute for Health and Care Excellence (NICE 2012) recommendations are discussed. Implications for nursing practice are also included, with a summary of sepsis in early infancy to aid the continued professional development of nurses working with young children in clinical settings.