Septic complications lead to a high mortality rate in very low birthweight infants (VLBWI). Therefore, prognostic markers for the development of sepsis attach importance to start an efficient therapy as early as possible. Functional and phenotypical variables of blood monocytes in the cord and peripheral blood were investigated to evaluate the parameters for predicting early-onset and late-onset sepsis (nosocomial infections). In a prospective study, 25 VLBWI were investigated. In the cord blood taken immediately after birth, the capacity of the monocytes to phagocytose non-opsonized E. coli bacteria by flow cytometry and the ex-vivo production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 (enzyme-linked immunoassay (ELISA)) after lipopolysaccharide (LPS) stimulation were measured. At the third day, the HLA-DR expression on the monocytes (flow cytometry) and the LPS-induced cytokine production were measured from the peripheral blood. Five VLBWI already developed early septic complications after 24-72 h, while the other three infants had late-onset sepsis 10-18 days after birth. The prognostic significance for early-onset sepsis was highest for the decreased monocyte phagocytic capacity (sensitivity and specificity: 100%) and for the LPS-induced formation of TNF-alpha and IL-1 beta in cord blood. Moreover, in septic VLBWI, the HLA-DR expression on the monocytes was lowered on day 3 after birth. The prognostic significance for late-onset sepsis was highest for TNF-alpha and IL-1 beta levels in the peripheral blood on the third day after birth. The determination of phagocytosis in the cord blood seems to be a reliable parameter for predicting early-onset sepsis and offers the possibility for a forward start of an antibiotic therapy.