OBJECTIVE:: Coagulase-negative staphylococci are the most common pathogens causing late-onset sepsis in the neonatal intensive care unit. Neonatal sepsis can be associated with cerebral white matter damage in preterm infants. Neurodevelopment has been shown to be correlated with apparent diffusion coefficients, fractional anisotropy, and axial and radial diffusivities of the white matter. DESIGN:: Prospective cohort study. SETTING:: Twenty-eight-bed neonatal intensive care unit at a tertiary care children's hospital. PATIENTS:: Seventy preterm infants (gestational age <32 wks), 28 with coagulase-negative staphylococcal sepsis (group 1) and 42 without sepsis (group 2). INTERVENTION:: The values of apparent diffusion coefficients, fractional anisotropy, and axial and radial diffusivity of three white matter regions (parietal, frontal, and occipital), estimated with diffusion-tensor magnetic resonance imaging with a 3.0-T magnetic resonance imaging system, were obtained at term-equivalent age. Neurodevelopmental outcome assessments were performed at 15 months (Griffiths Mental Developmental Scales) and 24 months (Bayley Scales of Infant and Toddler Development, Third Edition) corrected age. MEASUREMENTS AND MAIN RESULTS:: Values of apparent diffusion coefficients, fractional anisotropy, and axial and radial diffusivity of the left and right white matter regions were equal in all patients. There was no significant difference in apparent diffusion coefficient values (mean of total: 1.593 ± 0.090 × 10mm/sec and 1.601 ± 0.117 × 10mm/sec, respectively, p = .684), fractional anisotropy values (mean of total: 0.19 ± 0.04 and 0.19 ± 0.03, respectively, p = .350), radial diffusivity (mean of total: 1.420 ± 0.09 × 10mm/sec and 1.425 ± 0.12 × 10mm/sec, respectively, p = .719), and axial diffusivity (mean of total: 1.940 ± 0.12 × 10mm/sec and 1.954 ± 0.13 × 10mm/sec, respectively, p = .590) in the three combined regions between the two groups. No significant differences were found in neurodevelopmental outcome at 24 months. CONCLUSIONS:: No association was found between coagulase-negative staphylococcal sepsis in preterm infants and cerebral white matter damage as determined by values of apparent diffusion coefficients, fractional anisotropy, and radial and axial diffusivity at term-equivalent age, and no adverse effect was seen on early neurodevelopmental outcome.