Background: Multiple sclerosis (MS) is an autoimmune inflammatory neurodegenerative disease of the central nervous system and a major cause of disability in young adults. MRI is essential for diagnosis and monitoring, while early evaluation of structural brain changes is important. Aim: To evaluate brain volumetric changes using automated MRI analysis in patients with MS. Materials and Methods: This case–control study included 50 MS case patients and 50 controls patients examined between 2020–2023 at the Third State Hospital. T1-MPRAGE images were analyzed using volBrain automated segmentation software. Result: The mean age of MS patients was 45.5±11.8 years. Compared with healthy controls, the MS group showed significantly lower total grey matter volume (p=0.002), cortical grey matter volume (p<0.001), subcortical grey matter volume (p=0.006), and cerebral volume (p=0.02). Significant volume reductions were also observed in the temporal (p=0.006) and occipital (p<0.001) lobes. Deep grey matter structures, including the thalamus (p=0.001), caudate nucleus (p=0.009), putamen (p=0.008), and nucleus accumbens (p<0.001), also showed significantly reduced volumes. Disease duration was negatively correlated with total grey matter volume (r=−0.30, p=0.02), thalamic volume (r=−0.28, p=0.04), and occipital lobe volume (r=−0.43, p=0.002). Disease duration was also significantly associated with spinal cord involvement (p=0.01) and grey matter volume (p=0.04). The number of relapses was negatively correlated with total brain volume (r=−0.28, p=0.046). Conclusion Patients with MS demonstrated decreased grey matter volume, particularly within deep grey matter structures, along with increased abnormal white matter volume, suggesting the coexistence of neurodegeneration and demyelination in MS. Brain volume loss in MS appeared to occur independently of aging. Automated quantitative MRI analysis may provide important diagnostic value in detecting structural brain changes associated with MS.