Many therapies for DMD tested in dogs affected by Golden Retriever muscular dystrophy require immune response modulation. Cyclosporin and corticosteroids are known to improve dystrophic phenotype at anti-inflammatory dosages. However, the effects of this association at immunosuppressive levels must be characterized in GRMD dogs. In this aim, 5 GRMD dogs underwent CsA (20 mg/kg/d) and Prednisone (2 mg/kg/d) treatment starting at 2 up to 9 months of age. The consequences of the treatment on the dystrophic phenotype were assessed by clinical scoring and muscle biopsies. Effects on muscular function were examined using force measurements at 4, 6 and 9 months. Many side effects were observed, including growth retardation, overweight, extended papilloma, ectopic calcifications notably in the lungs, and luxations impairing locomotion. No evident influence of treatment on the clinical dystrophic phenotype was observed. Indeed, the clinical scoring evolution appeared heterogeneous, and superimposable to the range of scores of untreated GRMD dogs. Moreover, the treatment did not prevent hiatal hernias, a frequent consequence of diaphragmatic damages. The histological phenotype was not clearly improved, and intracellular calcifications were predominant. Force measurements showed that tetanic contraction force of the anterior compartment of the leg was decreased in comparison to untreated GRMD dogs. Moreover, the force decreased over time whereas it remained stable in untreated GRMD dogs, and increased in healthy dogs. This could be due to reversion of the type I predominance in treated dogs muscles, since the absence of dystrophin is known to impair type II more than type I fibers function. A muscle growth inhibition, due to calcineurin pathway blockade and corticosteroids could also be responsible for this loss of force. This study highlights deleterious repercussions of the association of CsA+Prednisone at immunosuppressive levels on GRMD dogs. These data are a keystone for the analysis of results in therapeutic trials. Thus, a force improvement can be interpreted with certainty as a gain of function due to the specific treatment, and not to the immunosuppressive regimen.