Background: Mpox–associated ocular disease, including keratitis, is an emerging, vision-threatening complication. Management is challenging because no anti-viral therapy has yet been approved to prevent permanent corneal scaring or blindness. Case presentation: We describe a 43-year-old female Ugandan health worker who acquired a Clade Ib mpox infection in July 2025 following occupational exposure during clinical examination of a patient with confirmed mpox attending a health facility in Kampala, Uganda. She developed severe ulcerative keratitis, with persistent epithelial defects and progressive stromal involvement despite standard-of-care treatment, including topical trifluridine and supportive therapy. Diagnostic confirmation of mpox was made by real-time polymerase chain reaction (PCR) from lesion swabs, and Clade Ib was identified. The keratitis remained active and vision-threatening for more than four months after symptom onset. Because of ongoing deterioration and high risk of irreversible vision loss, the treating team initiated topical cidofovir 0.5% ophthalmic drops under emergency compassionate use. Subsequent improvement included epithelial closure, decreased stromal inflammation, and visual recovery after 8 weeks of treatment and has since remained stable for to date. Conclusions: Topical cidofovir 0.5% may provide therapeutic benefit in severe, refractory mpox keratitis when trifluridine fails, and when no other effective, approved alternative exists. Controlled clinical evaluation and structured compassionate-use frameworks for cidofovir are urgently warranted given therisk of permanent blindness in mpox keratitis.