Some authors have suggested that when evaluating depression in multiple sclerosis (MS) patients, neurovegetative symptoms should be discounted and/or not considered, given the ostensibly high overlap between symptoms of MS (e.g., sleep disturbance, fatigue) and neurovegetative symptoms of depression. A further assertion is that inclusion of items assessing neurovegetative symptoms may artificially inflate overall depression scores and that mood scales may provide more accurate indices of depression in MS patients. The current study investigated the possibility that some neurovegetative symptoms may be specifically related to MS patients' depressed mood and are not simply indicators of physical disability and/or fatigue. Seventy-six clinically definite MS patients in the northwestern United States were administered two depression inventories and measures of physical disability and fatigue as part of a larger study. Results revealed that one neurovegetative symptom—disinterest in sex—was uniquely associated with depressed mood, and other neurovegetative symptoms were associated with both depression and fatigue but not physical disability. The present findings suggest that certain neurovegetative symptoms are differentially associated with depression, fatigue, and physical disability in MS. Routinely discounting all neurovegetative symptoms when assessing depression in MS patients may thus be unwarranted.