Neonates have an immature immune system with deficient complement activation, reduced neutrophil chemotaxis and phagocytic activity, limited immunoglobulin production (primarily relying on transplacental maternal IgG), and poor opsonization. Early-onset sepsis (EOS, within 72 hours of birth) is typically caused by vertical transmission of maternal organisms during labor and delivery. Group B Streptococcus (GBS) remains the most common pathogen, followed by E. coli. Inflammatory cascade activation causes cytokine release leading to vasodilation, capillary leak, and multi-organ dysfunction. Neonates may not mount a fever and instead present with hypothermia, reflecting their inability to generate an adequate inflammatory response.