In this paper we review the literature, present previously unpublished case reports for a pair of twins, and provide data from two prospective cohort studies to determine whether nasopharyngeal and/or endotracheal colonization with Ureaplasma urealyticum in preterm neonates is associated with an elevated white blood cell (WBC) count. We observed an association between colonization of the respiratory tract and elevation in the WBC count caused by an increase in the number of mature and immature neutrophils. Such a response indicates that U. urealyticum is capable of eliciting an inflammatory reaction and may be a true pathogen in the neonate. If these increases in the WBC count are confirmed, the WBC count may be a useful marker in future trials of interventions directed at U. urealyticum.