Invasive sepsis in the newborn period is a major cause of childhood morbidity and mortality worldwide. The infant immune system undoubtedly differs intrinsically from the mature adult immune system. Current understanding is that the newborn infant immune system displays a range of competencies and is developing rather than deficient. The infant gut mucosal immune system is complex and displays a plethora of phenotypic and functional irregularities that may be clinically important. Various factors affect and modulate the infant gut mucosal immune system: components of the intestinal barrier, the infant gut microbiome, nutrition and the maternal–infant hybrid immune system. Elucidation of the phenotypic distribution of immune cells, their functional significance and the mucosa-specific pathways used by these cells is essential to the future of research in the field of infant immunology.