A neonate with an estimated gestational age of 32 weeks who had post-partum sepsis (methicillin-resistant Staphylococcus aureus [MRSA] and Pseudomonas aeruginosa) and MRSA meningitis was found to have blunted light reflexes and microphthalmia in both eyes on routine screening for retinopathy of prematurity. Retrolenticular membranes precluded visualization of the fundi. Computed tomography confirmed the presence of intraocular calcifications, an interval development over 6 weeks from previously normal scans. Referral was made and diagnostic enucleation of the right eye was performed, revealing intraocular disorganization and metaplasia consistent with phthisis following intraocular inflammation. The patient's contralateral eye achieved visual acuity of light perception after lensectomy and vitrectomy. Vitreous cultures from the enucleation specimen and from the fellow eye at the time of vitrectomy were negative. Unsuspected, untreated endogenous endophthalmitis can result in dramatic and rapid metaplastic response in the developing eye and result in acute phthisis.