Background The aim of this study was to investigate any changes in mean platelet volume (MPV) in patients with neonatal sepsis (NS). Methods Subjects were stratified into two groups: proven sepsis (Group 1a) and clinical sepsis (Group 1b). The control group (Group 2) consisted of healthy newborns matched for gestational age and birth weight. Results A total of 100 patients with NS (35 with proven sepsis and 65 with clinical sepsis) and 50 healthy controls were enrolled. A comparison of markers of sepsis obtained at baseline revealed white blood cell count (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), and MPV levels to be significantly higher in newborns with sepsis compared to healthy controls (P = 0.01, <0.001, <0.001, and 0.001, respectively). Mean baseline serum levels of CRP and MPV were significantly higher in Group 1a compared to Group 1b (P = 0.003, P = 0.007, respectively), whereas the difference between group with regards to baseline serum levels of IL-6 and platelet count was statistically insignificant (P = 0.14, P = 0.28, respectively). Conclusion This is the first study to demonstrate a statistically significant difference with regard to baseline MPV values between patients with sepsis (proven or clinical) and healthy controls. J. Clin. Lab. Anal. 26:493-496, 2012. (C) 2012 Wiley Periodicals, Inc.