Purpose. To report a rapid endogenous fulminating panophthalmitis from Clostridium perfringens in a patient with diverticulitis and proliferative diabetic retinopathy. Methods. A 61-year-old female with poorly controlled diabetes mellitus, active proliferative diabetic retinopathy, and recent diverticulitis presented with conjunctival injection, ocular discharge, and sudden onset of painful vision loss of the left eye. Patient denied history of ocular trauma, intraocular surgery, or intravenous drug abuse. Examination revealed an erythematous, proptotic eye with restricted extraocular movements, mucopurulent discharge, diffuse corneal edema, and vitreous haze and cell. Orbital computed tomography (CT) confirmed no retained intraocular foreign body. Results. Despite 48 hours of treatment with systemic broad spectrum antimicrobial therapy (vancomycin, meropenem, and amphotericin B), patient underwent enucleation due to declined condition and progressive infection. Patient’s culture revealed gram-positive bacillus microbes (Clostridium perfringens). Patient’s subsequent CT abdomen showed resolved diverticulitis after antimicrobial therapy. Conclusion. Although rare, Clostridium perfringens infection can be a cause of rapid loss of vision from fulminate endogenous panophthalmitis. Urgent extensive systemic work-up to identify potential port of entry from visceral pathology and rapid removal of source of infection are pivotal to avoid high rate of mortality.