Coagulase-negative staphylococci are the most common cause of late-onset septicemia in neonates in intensive care nurseries. Clinical and laboratory diagnosis of infection with coagulase-negative staphylococci can be difficult. The authors reviewed serial mean platelet volumes of 18 infants in whom coagulase-negative staphylococci sepsis developed and found a significant increase in the mean platelet volume at the time of diagnosis and a return to baseline after resolution of the infection. The increase in mean platelet volume occurred although thrombocytopenia developed in only two of the infants and no difference was found in the mean platelet counts before and at the time of diagnosis of the infection. This finding may be a useful adjunct to the current laboratory tests used to diagnose coagulase-negative staphylococci sepsis in neonates.