Abstract Sepsis, a dysregulated host response to infection, has been difficult to accurately define in children. Despite a higher incidence, especially in neonates, a non-specific clinical presentation alongside a lack of verified biomarkers has prevented a common understanding of this condition. Platelets, traditionally regarded as mediators of haemostasis and thrombosis, are increasingly associated with functions in the immune system with involvement across the spectrum of innate and adaptive immunity. The large number of circulating platelets (approx. 150,000 cells per microlitre) mean they outnumber traditional immune cells and are often the first to encounter a pathogen at a site of injury. There are also well-described physiological differences between platelets in children and adults. The purpose of this review is to place into context the platelet and its role in immunology and examine the evidence where available for its role as an immune cell in childhood sepsis. It will examine how the platelet interacts with both humoral and cellular components of the immune system and finally discuss the role the platelet proteome, releasate and extracellular vesicles may play in childhood sepsis. This review also examines how platelet transfusions may interfere with the complex relationships between immune cells in infection. Impact Platelets are increasingly being recognised as important “first responders” to immune threats. Differences in adult and paediatric platelets may contribute to differing immune response to infections. Adult platelet transfusions may affect infant immune responses to inflammatory/infectious stimuli.