Introduction; MS is an inflammatory progressive disease with destruction of myelin sheath of neurons and axons. Among environmental risk factors HHV-6 might plays a role in MS. HHV-6 is a lymphotropic virus causing neurological symptoms. HHV-6 may exist in the PBMCs and CNS in a latent state. Materials and Methods; This case-control study was conducted on 116 new cases of MS whom naive to MS drugs. The control group consist 116 non-MS individuals whose gender, age and their place of residency were matched with the cases. Ten ml of peripheral blood was collected from each participant, their Sera and PBMCs were separated and the DNA was extracted from them separately. After Nested-PCR, the PCR products were sequenced. Statistical analysis of data was performed by V.22 of SPSS software and chi-square and Fisher’s exact tests and Odd‘s ratio were used. The P≤0.05 was considered as statistically significant. Results; considering of existence of HHV-6, there was a significant difference in PBMCs and Sera of case and control group, but among male participants the difference between cases and controls was not significant while this figure for female participants was significant in PBMCs and Sera. Regarding age group, only 21-25 and 31-35 groups were statistically significant. All positive samples were variant 6B of HHV-6. Discussion; HHV-6 can be considered as a MS risk factor mainly in female cases, especially in the age group of 20-35. HHV-6 is in its active state (Sera) in these patients.