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Background: Intrapartum antibiotics have reduced the incidence of neonatal early onset (EO) group B streptococcal (GBS) disease. Some surveillance data suggest that this success may be at the cost of increasing rates of non-GBS infection, especially in premature neonates., Objective: To examine rates of EOGBS infection and EO Escherichia coli neonatal sepsis in Australasia., Methodology: Analysis of trends in EO (<48 h age) GBS and E. coli sepsis from longitudinal prospective surveillance data collected from representative tertiary obstetric hospitals in each state of Australia and selected centers in New Zealand during a 10-year period from 1992 through 2001. Statistical analysis used Poisson regression., Results: 206 GBS and 96 E. coli cases occurred in 298,319 live births during the study period. The EOGBS sepsis rate fell from a peak of 1.43/1000 live births in 1993 to 0.25/1000 in 2001 (P < 0.001). The overall EO E. coli sepsis rate was 0.32/1000. In babies with birth weight <1500 g, it was 6.20/1000. There was an overall trend to decreasing EO E. coli sepsis (P = 0.07), and there was no significant change in E. coli sepsis in babies <1500 g (P = 0.60). Sixty-nine percent of E. coli cases occurred in the <1500 g cohort; the case fatality rate in this group was 50%. The overall case fatality rate from E. coli sepsis was 36%, and this rate remained stable during the study period (P = 0.47)., Conclusions: The increasing use of intrapartum antibiotics produced a steady decline in EOGBS disease in Australasia. There was also a trend to decreasing EO E. coli sepsis in all babies, and the rate in very low birth weight infants remained stable.