Systemic lupus erythematosus was diagnosed in a 3-year-old, male German Shepherd Dog. Clinical signs included lethargy, partial anorexia, fever, joint swelling, and skin and oral ulceration. The diagnosis was confirmed on the basis of an antinuclear antibody titer of 1:640 and immunofluorescence for immunoglobulin G at the dermal-epidermal junction in skin biopsy specimens. Treatment with prednisone and cyclophosphamide failed to induce remission. Intensive plasmapheresis-immunoadsorption, using purified Staphylococcus protein A in combination with low-dose prednisone therapy, resulted in sustained remission.