Within the multiple sclerosis (MS) population, high prevalence of psychiatric concerns, such as depression and anxiety, has been well documented. The purpose of this study was to examine factors contributing to higher depression and anxiety levels in a sample of 82 patients utilizing MS clinic services. Independent variables included MS physical severity, self-reported cognitive impairment, and perceived illness management, respectively. Results from hierarchical regression analyses indicated that depression was related to the physical severity, self-reported cognitive impairment, and perceived illness management variables. Anxiety was also related to the physical severity and self-reported cognitive impairment variables but not to the perceived illness management ones, suggesting that depression and anxiety symptoms may involve somewhat different processes within MS. The findings of this study support further clinical consideration and additional investigation of these variables in the treatment of anxiety and depression in an MS clinic population.