Objectives. To explore the association between meditation and health related quality of life (HRQOL), depression, fatigue, disability level, relapse rates, and disease activity in a large international sample of people with multiple sclerosis (MS). Methods. Participants were invited to take part in an online survey and answer questions relating to HRQOL, depression, fatigue, disability, relapse rates, and their involvement in meditation practices. Results. Statistically and potentially clinically significant differences between those who meditated once a week or more and participants who never meditated were present for mean mental health composite (MHC) scores, cognitive function scale, and health perception scale. The MHC results remained statistically significant on multivariate regression modelling when covariates were accounted for. Physical health composite (PHC) scores were higher in those that meditated; however, the differences were probably not clinically significant. Among those who meditated, fewer screened positive for depression, but there was no relationship with fatigue or relapse rate. Those with worsened disability levels were more likely to meditate. Discussion. The study reveals a significant association between meditation, lower risk of depression, and improved HRQOL in people with MS.