Osteomyelitis and septic arthritis are serious complications of sickle cell disease which occur at rates of 18% and 7%, respectively. In two small studies of osteomyelitis in sickle cell patients, the most common causative organisms were Salmonella spp. and Staphylococcus spp. Anaerobic infection is uncommon. Here, we report an 18-year-old girl with sickle cell disease and suspected spontaneous vertebral osteomyelitis due to Bacteroides fragilis. The diagnosis was based on multiple positive blood cultures. Despite extensive investigation, the port of entry could not be determined. The patient responded well to a four-week therapy with metronidazole, without the need for surgical debridement.