The present study aimed to describe the use of systemic mycophenolate as a steroid-sparing therapy for immune-mediated ophthalmic disease. Records for canine patients with suspected or confirmed immune-mediated ophthalmic disease were retrospectively reviewed for patient signalment, diagnoses, mycophenolate dose, concurrent medications, reported side effects, and long-term outcome while receiving systemic mycophenolate. Patient diagnoses included: anterior uveitis, panuveitis, presumed immune-mediated retinopathy, retinal detachment, chorioretinitis, optic neuritis, and/or uveodermatologic syndrome. Overall, 18 of 23 (78%) patients had either a complete or partial response to therapy. Only six of 18 (33%) patients with a complete or partial response to therapy continued to require adjunct systemic immunosuppressive/anti-inflammatory therapy. Gastrointestinal side effects were reported in five of 23 (22%) patients; one of these cases resolved with a 50% mycophenolate dose decrease while maintaining good control of intraocular inflammation. In conclusion, systemic mycophenolate may be considered as an adjunct or sole therapy for medical management of canine immune-mediated ophthalmic disease.