Cerebrospinal fluid (CSF) is an important sampling site for putative biomarkers and contains immune cells. CXCL10 is a multiple sclerosis (MS)-relevant chemokine that is present in the injured central nervous system and recruits CXCR3+ immune cells toward injured tissues. Perform a comprehensive evaluation to determine a potential relationship between CXCL10 and various immune cell subsets in the CNS of MS and control cases. In MS and control cases, CXCL10 was measured in the CSF and plasma by ELISA. Immune cells within both the CSF and peripheral blood were quantified by flow cytometry. Compared to non-inflammatory neurological disease (NIND) cases, MS cases had significantly higher CXCL10 in CSF (p = 0.021); CXCL10 was also correlated with total cell numbers in CSF (p = 0.04) and T cell infiltrates (CD3+, p = 0.01; CD4+, p = 0.01; CD8+, p = 0.02); expression of CXCR3 on peripheral immune cell subsets was not associated with CSF CXCL10. Elevated levels of CXCL10 in the CSF of MS cases are associated with increased T cells but appear to be independent of peripheral CXCR3 expression. These results support the importance of elevated CXCL10 in MS and suggest the presence of an alternative mechanism of CXCL10 outside of solely influencing immune cell trafficking.