The purpose of this study was to examine whether it is the invisible or the visible symptoms or signs of multiple sclerosis (MS) that are associated with greater health distress. Visible symptoms include the use of assistive devices, problems with balance, and speech difficulties, while invisible symptoms include fatigue, pain, depression, and anxiety. In a sample of 145 adults with MS, participants reported on these symptoms and their current level of self-reported health distress. Hierarchical regression analyses were used to determine whether invisible or visible symptoms were more predictive of health distress. When visible symptoms were added as the first step in the regression, 18% of the variance in health distress was explained. When invisible symptoms were added as the first step, 53% of the variance was accounted for. The invisible symptoms of pain and depression were the most significant predictors of distress. For a subset of the sample that had had MS for more than 11 years, pain and depression continued to be important predictors, but assistive-device use and fatigue were also important. Nurses should be aware that invisible symptoms may be more troubling to patients than visible symptoms and should ensure that adequate screening and treatment are provided for those with MS.