This case illustrates the rare presentation of endogenous Klebsiella pneumoniae endophthalmitis with concomitant orbital cellulitis from an acute pyelonephritis. A 59-year-old Caucasian female with type 2 diabetes mellitus was transferred from a regional hospital with decreased visual acuity, periorbital edema, photophobia, proptosis and pain of the right eye, as well as suprapubic discomfort. Initial ocular examination and B-scan ultrasonography were consistent with endophthalmitis and orbital cellulitis which lead to a vitreous tap and intravitreal antibiotics injection and systemic antibiotherapy. Vitreous and blood cultures confirmed Klebsiella pneumoniae as the causative organism. An orbital MRI showed a panophthalmitis with optic neuritis and further imaging confirmed a concomitant pyelonephritis secondary to a septic nephrolithiasis. The patient was given treatment with high-does intravenous antibiotics, oral and topical corticotherapy, and an early core pars plana vitrectomy (PPV), performed 5 days after presentation with repeat injections of antibiotics and dexamethasone. Unfortunately, two weeks following PPV, despite an initial stable postoperative course, the patient deteriorated and presented with purulent discharge from one of the vitrectomy port incision site. An emergency evisceration was performed in order to control the infection, revealing a large subretinal abscess and necrosed sclerotic tissue around the prior vitrectomy incision sites. Conclusion: This is the first case report of Klebsiella pneumoniae endophthalmitis or panophthalmitis presenting with orbital cellulitis and optic neuritis from an urinary tract infection. Prognosis is poor despite treatment including early vitrectomy.