Subpalpebral lavage systems (SPLSs) were adapted for use in zoo llamas (Lama glama) and a wild harbor seal (Phoca vitulina) during therapy for severe ulcerative keratitis or corneal perforation. One llama presented with a melting corneal ulcer caused by Pseudomonas aeruginosa, which necessitated frequent application of a topical ophthalmic antibiotic. The lavage system was used routinely during the day and was connected to a balloon infusion system at night to allow for continuous medication administration. The ulcer healed soon after therapy was extended to include overnight treatment with the infusion system. A SPLS system was also combined with a balloon infusor during postoperative treatment of a second llama that had sustained a corneal perforation. Both llamas tolerated the infusor/lavage systems well and regained vision. One llama had minor conjunctival irritation from the SPLS that resolved quickly without treatment. Bilateral SPLS were placed in a wild harbor seal for treatment of severe ulcerative keratitis associated with Candida albicans infection. The seal tolerated the lavage systems well throughout 14 wk of their use in an aquatic environment with other seals. Partial detachment of the lavage systems from the skin of the seal occurred a few times during treatment and was easily corrected. Severe keratitis resolved with administration of antimicrobials through the lavage systems, and the seal was returned to the wild. The use of SPLSs alone or in combination with balloon infusion systems warrants consideration for exotic, wild, and aquatic animals that cannot tolerate repetitive manual applications of topical ophthalmic medication.