OBJECTIVES: Existing assessments of the health related quality of life (HRQoL) in patients with multiple sclerosis have focused on persons with the disease. What has not been assessed is the extent to which the presence of multiple sclerosis generates HRQoL deficits compared to the general population.  METHODS: Data are from the internet-based 2008 National Health and Wellness Survey in the UK, France, Spain, Italy and Germany. A total of 53,524 respondents completed the survey form, of whom 308 indicated they had a diagnosis of multiple sclerosis. Respondents completed the SF-12 generic HRQoL instrument. The analysis is based on the summary mental component scores (MCS), physical component scores (PCS) and health state utilities from the SF-6D items derived from the SF-12 instrument. A multivariate analysis (using ordinary least squares) was undertaken with the MCS, PCS and SF-6D utilities as dependent variables. The independent variables included a binary variable for the presence/absence of multiple sclerosis, socio-demographic characteristics, health risk factors (e.g., body mass index), country dummy variables and the Charlson Comorbidity Index (CCI).  RESULTS: Persons reporting multiple sclerosis had substantially lower PCS scores (32.19 vs. 48.66; t=24.60); MCS scores (39.78 vs. 46.53; t = 10.18) and utility  scores (0.57 vs. 0.72; t=23.57). In the multivariate modeling, the deficit associated with the presence of multiple sclerosis was substantially greater than any other independent variable in the PCS (-12.07; 95% CI: -14.02 to -10.12) and utility models (-0.11; 95% CI: -0.13 to -0.09).  The utility decrement in the SF-6D model attributed to multiple sclerosis far outweighed the utility deficits attributable to the other independent variables. CONCLUSIONS: Compared to the non-multiple sclerosis population, there are substantial HRQoL deficits associated with the diagnosis of multiple sclerosis. These deficits are substantial and far outweigh those attributable to socio-demographic characteristics, health risk factors and the presence of comorbidities.