BACKGROUND Serratia marcescens infections have historic association with injection drug use. The present report is about a 53-year-old man with a history of intravenous (IV) drug use who presented with acute loss of vision due to endophthalmitis associated with disseminated S. marcescens infection. CASE REPORT A 53-year-old man with a history of active illicit IV drug use presented with a chief complaint of loss of vision in his left eye for 5 days. He also reported having a fever, chills, and shortness of breath. While in the Emergency Department, he became hypotensive and hypoxic. He needed to be intubated and was started on vasopressor support. An ophthalmological examination was suspicious for endophthalmitis. The patient underwent a vitreous tap with injection of intravitreal antibiotics on the day of admission. An echocardiogram showed severe tricuspid endocarditis requiring valve replacement. He also was found to have a left lung/pleural abscess, which was surgically drained. Later, a left eye vitrectomy was performed and the intravitreal antibiotics were repeated; the treatment was unsuccessful and enucleation eventually was required. In addition, the patient had gastric bleeding and underwent esophagogastroduodenoscopy, which showed ischemic stomach ulcers suggestive of septic emboli. Cultures of the patient's blood, tricuspid valve, lung abscess, and vitreous fluid revealed S. marcescens. He was treated long term with a 2-drug antibiotic regimen and discharged in stable condition. CONCLUSIONS We have presented a rare case of acute loss of vision due to endophthalmitis in a patient with a history of IV drug use, which was associated with disseminated infection with the Gram-negative saprophyte S. marcescens.