Study objective: Bacteremic periorbital cellulitis has traditionally been associated with Haemophilus influenzae infection, and the recommended diagnostic evaluation in young children includes blood culture and cerebrospinal fluid (CSF) analysis. The objectives of this study were to examine in pediatric patients with periorbital cellulitis (1) the prevalence of H influenzae bacteremia in the era of vaccination for H influenzae type B (HIB) and (2) the yield of routine CSF analysis. Methods: This was a retrospective case series of children aged 2 months to 17 years with a final discharge diagnosis of periorbital cellulitis who were treated from 1986 through 1994 at an urban university referral hospital. The prevalence of bacteremia and meningitis was obtained from chart review. Results: Forty-nine children were enrolled, of whom 3 were treated as outpatients. The mean age was 36 months (median, 19 months). A blood culture was obtained for 92% of the patients. Five patients (10%; 95% confidence interval, 3% to 22%) had a positive blood culture (four streptococcal species, one H influenzae). The patient with H influenzae bacteremia was treated in 1987 and had not had the HIB vaccine. CSF was analyzed for 41% of the patients, and none had an abnormal cell count or a positive culture. Sinusitis was diagnosed radiographically in 19% of the subjects. Conclusion: Streptococcal organisms are the most common cause of bacteremia associated with periorbital cellulitis in the post-HIB vaccination era. H influenzae bacteremia is now a rare occurrence. Meningitis is uncommon, and lumbar puncture may not be mandatory in well-appearing children. Sinusitis is common and was probably underdiagnosed in our series because most children were not evaluated radiographically. Outpatient management may be indicated in selected children. [Schwartz GR, Wright SW: Changing bacteriology of periorbital cellulitis. Ann Emerg Med December 1996;28:617-620.]