Background Penile enhancement with injectable agents is a rising trend and yet has received little scientific attention despite the potential for serious complications. These include cosmetic, functional and systemic complications that may require complex penile reconstructive surgery. We report a case of delayed severe infection following penile filler insertion leading to multi-organ failure and intensive care support. Case presentation A 31-year-old man presented with fevers and progressive pain and swelling of the penile shaft, 3 days after unprotected sexual intercourse. The patient received subcutaneous hyaluronic filler injections at a cosmetic clinic for penile enlargement two months prior to presentation. Relevant social history include polysubstance abuse and multiple sexual partners. Physical examination revealed gross penile oedema and erythema, with a ventral curvature of the penile shaft and a superficial abrasion on the distal ventral penile shaft. Within 24 h the patient developed septic shock with anuria, hypotension and fevers to 40 °C, requiring transfer to the Intensive Care Unit (ICU) for vasopressor and inotropic support. Intraoperative penile exploration revealed multiple pus stained fillers which were drained and grew Streptococcus Pyogenes on cultures. There was no abscess or evidence of necrotising fasciitis intraoperatively. The patient improved with intravenous antibiotics and was stepped down from the ICU after four days and discharged on day eight. One month post admission there was significant superficial skin loss to both ventral and lateral aspect of the penis, with healthy granulation tissue at the base. The patient opted for conservative management with regular dressings. He reported normal sexual and urinary function three months post admission. Conclusion This is the first published case of sepsis from a penile infection in the context of hyaluronic acid penile fillers. In an era of escalating demand for penile cosmetic procedures, there is an increasing need for early recognition and appropriate management of penile filler infections. We report an unusual case of a localised penile infection rapidly progressing to sepsis with multi-organ failure requiring intensive care support. The case demonstrates early surgical intervention with targeted antimicrobials can result in successful eradication of infection, with satisfactory cosmetic and functional outcomes for patients.