Background Cutibacterium acnes is the most common pathogen in shoulder prosthetic joint infections. Short-contact benzoyl peroxide (BPO) solutions effectively reduce C acnes loads on the shoulder preoperatively. It is unknown how long the effect of BPO lasts. We evaluated C acnes counts 1 week after BPO application. We hypothesized that BPO would decrease C acnes burden with a rebound after 1 week. Methods Screening of 102 healthy volunteers with no history of shoulder surgery or C acnes infection was performed to establish bacterial counts. Thirty-four participants were selected based on an established threshold. Each was given BPO 5% for 3 consecutive days of application on either the left or right shoulder as indicated by a random number generator. Deep sebaceous gland cultures were obtained with a detergent scrub technique before BPO application, after 3 days of use, and 1 week after BPO treatment commenced. Results The differences between the logarithmic reduction and the logarithmic rebound at the anterior, lateral, and posterior sites were statistically significant. Anteriorly, the average log reduction was −0.44 and the average log rebound was 0.69 (P = .003). Laterally, reduction was −0.64 and rebound was 0.74 (P = .003). Posteriorly, reduction was −0.63 and rebound was 0.78 (P = .008). At the axilla, reduction was −0.40 and rebound was 0.31 (P = .10). The differences in C acnes burden between pretreatment and 1-week counts at all sites were not statistically significant. Conclusion A significant decrease in C acnes burden occurred after BPO application but was not permanent. Significant rebound occurred just 1 week later.