Iron deposition has been noted widely in the subcortical deep gray matter (SDGM) of multiple sclerosis (MS) patients. Recent evidence suggests that serum iron may cross the blood–brain barrier and might be associated with SDGM iron deposition. The aim of the current study was to assess whether an iron-sensitive MRI measure is related to serum iron concentrations. This was a retrospective, cross-sectional study of 22 MS patients and 24 healthy controls (HCs), group matched for age and sex. Participants were imaged on a 1.5-T MRI scanner. High-resolution T1-weighted images and susceptibility-weighted images were acquired for assessing SDGM volumes and iron deposition within the SDGM, respectively. All participants also had blood drawn for the measurement of serum iron concentrations. MS and HC groups were compared with respect to SDGM tissue volumes and iron content. Partial correlations, controlling for age, sex, and structural volume, were used to assess the relationship between serum iron and SDGM iron content. MS patients presented with significantly smaller SDGM tissue volumes of the caudate, globus pallidus, putamen, and thalamus (all P≤0.0001). With respect to HCs, increased iron content was observed for MS patients in the globus pallidus (P=0.009) only. In MS patients only, there was a significant relationship between serum iron and putaminal iron volume (partial r=0.449, P=0.041), whereas trends were evidenced for the caudate (partial r=0.396, P=0.078) and the globus pallidus (partial r=0.410, P=0.065). Serum iron content in MS patients may be related to SDGM iron content. These results warrant confirmation in a larger study of MS patients.