BACKGROUND AND PURPOSE: Healthy lifestyle behaviour modification may improve health outcomes in people with multiple sclerosis (pwMS), but empirical evidence is needed to confirm prior study findings. We developed an online multimodal lifestyle intervention (Multiple Sclerosis Online Course) to examine the impact of lifestyle modification on health outcomes in pwMS via a randomized control trial (RCT). However, the present study specifically analyses baseline data to assess engagement with healthy lifestyles by RCT participants and cross-sectional associations with health outcomes. METHODS: Baseline engagement with six "healthy lifestyle behaviours" of the intervention course (high-quality, plant-based diet; ≥5000 IU/day vitamin D; omega-3 supplementation; ≥30 min physical activity 5 times/week; ≥30 min/week meditation; and nonsmoking) was examined. Associations between individual versus collective behaviours (individual behaviours summated) and health outcomes (quality of life [QoL]/fatigue/disability) were evaluated using multivariate modelling (linear/log-binomial/multinomial). RESULTS: At baseline, 33.7% and 30.0% of participants (n = 857) engaged in one or two healthy behaviours, respectively. In total, engagement with healthy lifestyles by participants was as follows: nonsmoking, 90.7%; omega-3 supplementation, 34.5%; vitamin D supplementation, 29.8%; physical activity, 29.4%; diet, 10.7%; and meditation, 10.5%. Individual behaviours (nonsmoking/physical activity/diet) were independently associated with better health outcomes. Engagement with multiple behaviours, especially diet and physical activity, was associated with better outcomes; engaging with ≥4 behaviours was associated with a 9.0-point higher mental QoL and a 9.5-point higher physical QoL, as well as 23% and 56% lower prevalence of fatigue and moderate disability, respectively. CONCLUSIONS: Baseline engagement with ≥4 healthy behaviours, including diet and physical activity, was associated with better health outcomes.