Sexual dysfunction (SD) is frequently reported in multiple sclerosis (MS) and is likely related to MS-related damage to the spinal cord (SC). To assess associations between SD and quantitative MRI measures in people with MS (pwMS). This pilot study included 17 pwMS with SD who completed questionnaires assessing SD, mood, and fatigue. All participants underwent brain, cervical, and thoracic SC-MRI at 3T. Quantitative brain and SC-MRI measures, including brain/SC atrophy, SC lesion count, diffusion-tensor imaging (DTI) indices (fractional anisotropy [FA], mean, perpendicular, parallel diffusivity [MD, λ⊥, λ||]) and magnetization-transfer ratio (MTR) were obtained. Associations between quantitative MRI measures and SD were assessed while controlling for the extent of mood and fatigue symptomatology. Subjects were a mean age of 46.9 years and 29% female. All subjects had self-reported SD (MSISQ-19 = 40.7, SQoL: 55.9) and 65% had a concurrent psychiatric diagnosis. When correlations between SD severity were assessed with individual brain and SC-MRI measures while controlling for psychiatric symptomatology, no associations were found. The only variables showing independent associations with SD were anxiety (p = 0.03), depression (p = 0.05), and fatigue (p = 0.04). We found no correlations between quantitative MRI measures in the brain and SC and severity of SD in pwMS, but psychiatric symptomatology and fatigue severity demonstrated relationships with SD. The multifactorial nature of SD in pwMS mandates a multidisciplinary approach.