Diagnosis of early-onset neonatal infection has led to the development of several screening tests including C-reactive protein, a very commonly used marker, and cytokines (mainly interleukin-6 and -8), alone or in combination with C-reactive protein, based on the premise that their increases in response to infection may precede that of C-reactive protein. In recent years the search for diagnostic tests has turned to procalcitonin, a propeptide of calcitonin, which appears to be a promising marker of infection in newborn infants. Additionally, specific leukocyte cell surface antigens (mainly CD11b and CD64), detected by flow cytometry, are evaluated as markers of neonatal infection, since their expression on the cell membrane increases in substantial quantities after leukocyte activation by bacteria or their cellular products. This review aims to examine the role of these newly available immunologic indices and to assess their validity as diagnostic markers of infection during the neonatal period.