Individuals with multiple sclerosis (MS) may experience symptoms that impact comorbid conditions and quality of life (QOL). There is some evidence that symptom severity may vary in certain common health conditions in this population. We aimed to examine symptom severity in light of comorbid conditions commonly seen in individuals with MS (N = 339). Using a cross-sectional Internet survey, we found there was a significant increase in symptom severity of common symptoms of fatigue, imbalance, and weakness, specifically with presence or absence of certain comorbid conditions (depression, arthritis, migraine headaches, coronary artery disease [CAD]). These findings endorse the presence of more severe symptoms with certain comorbid conditions compared with individuals with MS who do not report having comorbid conditions. The findings support the importance of symptom management in individuals with MS who also have comorbid conditions.