OBJECTIVE: Premature infants can experience cardiorespiratory events such as apnea after immunization in the neonatal intensive care unit (NICU). These changes in clinical status may precipitate sepsis evaluations. This study evaluated whether sepsis evaluations are increased after immunizations in the NICU. STUDY DESIGN: We conducted a retrospective cohort study of infants older than 53 days who were vaccinated in the NICU at the KPMCP (Kaiser Permanente Medical Care Program). Chart reviews were carried out before and after all immunizations were administered and for all sepsis evaluations after age 53 days. The clinical characteristics of infants on the day before receiving a sepsis evaluation were compared between children undergoing post-immunization sepsis evaluations and children undergoing sepsis evaluation at other times. The incidence rate of sepsis evaluations in the post-immunization period was compared with the rate in a control time period not following immunization using Poisson regression. RESULT: A total of 490 infants met the inclusion criteria. The rate of fever was increased in the 24 h period after vaccination (2.3%, P<0.05). The incidence rate of sepsis evaluations was 40% lower after immunization than during the control period, although this was not statistically significant (P=0.09). Infants undergoing a sepsis evaluation after immunization were more likely to have an apneic, bradycardic or moderate-to-severe cardiorespiratory event in the day before the evaluation than were infants undergoing sepsis evaluations at other times (P<0.05). CONCLUSION: Despite an increase in fever and cardiorespiratory events after immunization in the NICU, routine vaccination was not associated with increased risk of receiving sepsis evaluations. Providers may be deferring immunizations until infants are clinically stable, or may have a higher threshold for initiating sepsis evaluations after immunization than at other times.