Background Theory of mind (ToM) is one of the several different concepts in social cognition and is defined as the ability to access the mental states of others or to adopt the point of view of others. Although studies have shown that ToM is impaired in people with multiple sclerosis (MS), the results based on individual ToM tasks are conflicting; some studies have shown deficits only in the ‘Reading the Mind in the Eyes’ Test (RMET), while others have reported poor performance in the Faux Pas Test (FPT) as well as RMET. Furthermore, little is known about the relationship between ToM performance and neuroanatomical characteristics in MS. This study investigated ToM impairment and its relationship to regional brain volume or cortical thickness in people with MS.Methods This cross-sectional study included 20 participants with relapse-onset MS and 27 age- and sex-matched volunteers as healthy controls (HC). All the participants underwent neuropsychological (NP) tests as well as ToM tasks, including RMET and FPT. Participants with MS underwent brain MRI within 6 months before and after undergoing the NP and ToM tests. Regional volume of subcortical structures or cortical thickness were analysed based on 3D T1-weighted images using FreeSurfer software.Results Both RMET and FPT scores were significantly lower in participants with MS than in HC (p = 0.0049, p = 0.0071, respectively). Imaging analyses showed that FPT scores, but not RMET scores, were positively correlated with the right thalamus (R2 = 0.26, p = 0.012) and left pallidum (R2 = 0.39, p = 0.0021) volumes after adjusting for age. Furthermore, surface-based morphometry revealed significant correlation between age-adjusted cortical thickness of ten cortical areas, including the fusiform gyrus, orbitofrontal cortex, temporal–parietal junction, and superior temporal gyrus, and FPT scores.Conclusions These study findings showed that both RMET and FPT performances are impaired in participants with MS. Furthermore, FPT deficits, but not RMET deficits, were significantly associated with the volume of two subcortical structures as well as the thickness of ten cortical areas, suggesting that FPT is an appropriate task to access ToM performance in MS.