Introduction: Total knee arthroplasty (TKA) is a widely performed elective procedure globally. Periprosthetic joint infection (PJI) remains a serious complication following TKA. Hematogenous seeding from distant infections is a recognized mechanism of PJI. However, to our knowledge, there are no published reports of hematogenous PJI originating from acute epididymo-orchitis. Case Report: A 74-year-old male presented to the emergency department following a ground-level fall on his right knee. He was diagnosed with a knee effusion and discharged for outpatient follow-up. Approximately one week later, the patient presented to his primary care physician with right scrotal swelling and was diagnosed with epididymitis and started on oral antibiotics. The following day, he underwent right knee arthrocentesis which was positive for an acute PJI. The patient then underwent a double debridement, antibiotics and implant retention (DAIR) procedure and was discharged on a six-month course of oral antibiotics. Eight months after the double DAIR, the patient developed right knee swelling and erythema. Right knee aspiration was positive for a persistent PJI, and the patient underwent resection arthroplasty with insertion of an antibiotic spacer. Conclusion: Hematogenous spread of epididymoorchitis resulting in PJI is a rare and underreported complication that has not been fully understood in the literature. In this case, several risk factors—such as the presence of a prosthetic joint, recent trauma, and chronic corticosteroid use—may have increased the patient’s susceptibility to infection. Close monitoring of inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, and white blood cell count can aid in the early detection of septic arthritis and contribute to improved patient outcomes.