Objective: This study examined individual and co-occurring behavioral risk factors (diet, exercise, and stress) in wheelchair users with multiple sclerosis (MS) and potential association with MS symptoms (ie, fatigue, depression, anxiety, pain, sleep, and health-related quality of life [HRQOL]). Design: Survey. Setting: General Community. Participants: One hundred twenty-three wheelchair users with MS completed this study (N=123). Interventions: Not applicable. Main Outcome Measures: Participants were mailed instructions for accessing online questionnaires (demographic and clinical characteristics, Godin Leisure-Time Exercise Questionnaire, Perceived Stress Scale, Automated Self-Administered 24-Hour Dietary Assessment Tool, and MS symptoms). Results: Standard cut-points were used to categorize behavioral risk factors and then identify the extent and distribution of these behaviors both individually and co-occurring. We then analyzed the associations between behavioral risk factors and MS symptoms using bivariate correlation analyses and Mann-Whitney U tests. The mean age of participants was 60.6 +/- 10.0 years, 76% identified as women, 82% had a progressive disease course, and the mean MS duration was 23.0 +/- 9.7 years. Seven participants were classified as having 0 negative health behaviors, 41 participants had 1 negative health behavior, 49 participants had 2 negative health behaviors, and 26 participants had 3 negative health behaviors. The number of negative health behaviors was significantly correlated with HRQOL (physical, r=.30; psychological, r=.47), sleep (r=.25), depressive symptoms (r=.36), and anxiety (r=.43). Mann-Whitney U tests indicated greater fatigue, depression, and anxiety as well as lower sleep quality and HRQOL among participants who reported 2 or 3 behavioral risk factors compared with 0 or 1 behavioral risk factor. Conclusions: Future research should examine the design and implementation of multiple health behavior change interventions targeting co-occur-ring behavioral risk factors among wheelchair users with MS. Archives of Physical Medicine and Rehabilitation 2023;104:590-6 (c) 2023 by the American Congress of Rehabilitation Medicine.