This prospective study reports on screening for neonatal sepsis among 3,372 live births out of 6,060 consecutive deliveries at the University Hospital of Pointe-à-Pitre, Guadeloupe, during a 30-month period. Group B Streptococcus (GBS) was the most common pathogen, representing 46% (89/194) of positive blood cultures and 52% (335/637) of positive gastric aspirates. Although only 3,372 (55%) of all live births were screened, 637 (10%) had gastric bacterial carriage at birth; of those, 335 (5.5%) involved GBS. Similarly, there were 194 (3.2%) positive blood cultures, of which 89 (1.5%) involved GBS. In this report, all newborns who presented with a positive GBS blood culture had at least one of the external tests positive for GBS (gastric, ear canal, rectum and placenta). Thirty-seven per cent (14/38) of positive neonatal blood cultures occurred in newborns with foetid liquor while in deliveries with intrapartum fever 16.5% (32/195) of blood cultures were positive. In our clinical practice, characteristics that were evident in the delivery room (without knowledge of prenatal follow-up) such as foetid liquor, intrapartum fever, prolonged rupture of membranes, foetal tachycardia and meconium staining were associated with the great majority of neonatal sepsis.