Escherichia coli is the second most common bacterium isolated from the blood of neonates with sepsis. During a 12-year period from January 1988 through December 2000, E. coli sepsis or central nervous system infections were diagnosed in a total of 46 infants (M/F ratio, 3.6:1) in a tertiary care medical center. These infants were stratified into 3 groups according to age at disease onset. Group A include infants at birth to 7 days old; Group B, 7 days to 1 month old; and Group C, beyond 1 month old. Among them, 13 had sepsis, 24 had urosepsis, and 9 had meningitis or meningoencephalitis. All patients with central nervous system infections were younger than 40 days old. In the urosepsis group, 22 (91.7%) of 24 patients were younger than 6 months old with a male predominance (M/F ratio, 20:4), and 7 (29.2%) of 24 had urinary tract anomaly. Nine (68%) of 13 patients with sepsis had underlying disease. The most common clinical signs and symptoms were fever (89.1%), followed by tachycardia (71.7%), ill looking (50%), poor feeding (30.4%), and tachypnea (23.9%). The significant laboratory findings were elevated C-reactive protein (60.9%), and leukocytosis (56.5%) with left shifting (43.5%). Antimicrobial susceptibility test of the isolates showed a 67.7% resistant rate to ampicillin and a 35.5% resistant rate to chloramphenicol between 1994 and 2000. No significant increase in the resistance rate of the strains was noted compared with results from 2 studies conducted at different periods of time (1988-1993 and 1994-2000). Two infants with central nervous system infection died and 5 experienced major neurological sequelae. The clinical spectrum of invasive E. coli infections is age-related and associated with the underlying conditions. The prognosis was related to the development of central nervous system complications.