Newborn sepsis is the clinical syndrome characterized by bacteremia with systemic signs and symptoms of the infection in the first 4 weeks of life. Bacteria and viruses are the most common causes of an infection, while fungi and parasites, in spite of sporadic phenomena, play an important role in the etiology of newborns sepsis. There are two main sources of newborn infections: mother and hospital environment. The most common causes of early - onset newborn sepsis in term and preterm neonates are Streptococcus Group B Streptococcus agalactiaei and Escherichia Coli, while most common causes of late - onset newborn sepsis are coagulase - negative Staphylococci, Gram - negative Bacilli and fungi. Newborns with symptoms and signs of sepsis require rapid assessment, diagnosis and antibiotic treatment. Since the symptoms of newborn sepsis are often unspecific, diagnostic should be part of the evaluation of an each neonate with risk factors or symptoms that may be associated with sepsis. Prevention of newborn sepsis can be directed into procedures for control of early - and late – onset sepsis with an emphasis on the application of guidelines and protocols in everyday work during all care procedures for healthy and sick newborns. Success can only be achieved by teamwork. A key readiness is to change behaviours and apply new insights into the infection control.