Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating disorder of the central nervous system (CNS) characterized by demyelination and axonal degeneration. Corpus callosum (CC) is commonly involved during the disease process leading to atrophy (93%). Currently, there are no established markers of disease progression and the interplay of processes leading to brain atrophy in MS remains unknown. The primary aim of this study was to assess the frequency of CC atrophy in MS patients. Furthermore, the relationship between expanded disability status scale (EDSS) and transcranial magnetic stimulation (TMS) evoked motor potentials (MEP) were assessed to capture disease effects by independent parameters. Seventy-nine MS patients and 50 controls were included and their CC volumes were assessed. Out of 79 patients, 31 patients (39·2%) had CC atrophy. The distribution of EDSS scores among the group with CC atrophy [13 (32%) patients with EDSS 0-2; 11 (58%) patients with EDSS 2-4; 19 (24%) patients with EDSS ≥4] was not statistically significant (p>0·05). MEP latency was abnormal in 34 (43%) patients, 67 (85%) patients had abnormal MEP amplitude and CMCT was abnormal in 32 (41%) patients. The relation between EDSS and MEP was statistically significant among the patient population including the subgroup of patients with CC atrophy (p<0.05). Our results lacked to provide an association between disability and CC atrophy, but there was a correlation between CC atrophy and TMS evoked motor potentials. Early evolution of axonal degeneration and brain atrophy should be considered in terms of follow-up measures to provide long-term efficiency impacting disability, progression and brain atrophy.