1) Purpose: Pediatric musculoskeletal infections can be devastating, with ramifications that can cause lasting morbidity. Children often receive antibiotics in various clinical settings prior to having cultures obtained. A commonly held notion is that administration of antibiotics prior to obtaining samples from the involved musculoskeletal site will result in negative cultures. The purpose of our study was to evaluate whether or not culture results for children receiving antibiotics prior to obtaining cultures for suspected septic arthritis and/or osteomyelitis is negatively affected. We hypothesize that antibiotic administration prior to bone and/or joint culture in children with suspected osteomyelitis or septic arthritis would result in a greater number of negative cultures. 2) Methods: A retrospective chart review of 107 children was performed at a single institution. Children age < 18 years with suspected osteomyelitis or septic arthritis that received antibiotic administration (oral or intravenous) within seven days of obtaining a formal culture were included. Comparison based on pre-sample antibiotic administration and final culture results were made as well as the recording of frequency and type of antibiotic, organisms isolated, blood cultures, diagnoses, location of infection, age, sex, fever, WBC, ESR, and CRP. 3) Results: 107 children, with an average age of 8.2 years old (0-16) were included. 59/107 (55%) patients received antibiotics prior to culture. Patients who received antibiotics prior to obtaining a sample were more likely to have positive results. Children with positive blood cultures regardless of timing to antibiotic administration had a higher maximum fever than those with negative cultures. 4) Conclusion: Receiving antibiotics prior to obtaining cultures did not lead to a statistically significant number of negative cultures. Patients who received antibiotics prior to tissue/joint sample were more likely to have positive cultures. Delaying antibiotic treatment until formal samples were obtained demonstrates no benefit for diagnostic purposes.