Periprosthetic joint infection (PJI) was the leading cause of artificial joint replacement failure. The aim was to determine antibacterial activity of a novel titanium–copper (Ti–Cu) sintered alloy in vivo. S. aureus suspension was used to construct rabbit models with PJI. The inflammation and infection condition was evaluated by animal survey, bacteria number radiographic examination and histological examination. The levels of white blood cell (WBC), interleukin 6 (IL-6) and C-reactive protein (CRP) were measured to evaluate inflammation. After implantation, serious inflammation with purulent exudate was found in Group II (Ti/Ba), and mild infection was found in Group I (Ci–Ti/Ba). The WBC, IL-6 and CRP levels in Group I were significant higher compared with Group II after implantation. Bacterial incubation results showed that the amounts of S. aureus in Group I were lower compared with Group II after implantation. Radiographic and histological examination also showed that obvious bone destruction was observed in Group II, while not in Group I. Overall, this novel Ti–Cu sintered alloy presented strong antibacterial activity than traditional Ti-based orthopedic materials, suggesting that it has potential to become an ideal antibacterial material for orthopaedic implantation to reduce PJI or implant-related inflammation.