Although a few cases of dermatitis or keratitis caused by exposure to the sap of Euphorbia trigona have been reported, we present a rare case of transient corneal endothelial dysfunction following exposure to the sap, resulting in corneal edema. A woman in her 70s complained of reduced vision, redness, and teariness in her left eye 2 days after exposure to the sap of E. trigona at home. Upon examination, hyperemia, serious corneal edema, and anterior uveitis with hypopyon were observed in her left eye, without corneal epithelial defects or keratic precipitates. The best-corrected visual acuity (BCVA) was 2.0 (logarithm of the minimum angle of resolution), and the measured central corneal thickness (CCT) was 812 µm. The patient was treated with topical instillation of 1.5% levofloxacin and 0.1% dexamethasone to reduce intraocular inflammation and corneal edema. Three weeks later, the BCVA reached 0, the CCT was 519 μm, and the corneal endothelial cell density was 3,233 cells/mm2. Six months after the injury, the patient had good visual acuity, and the cornea was completely transparent. No recurrence of corneal edema or anterior uveitis was observed. Exposure to the sap of E. trigona can lead to severe corneal edema with anterior uveitis, impairing visual acuity. Taking precautions to prevent the exposure of the eye to the sap of this plant is crucial.