Twenty-nine patients with secondary progressive MS underwent monthly assessment with Expanded Disability Status Scale (EDSS), MS Functional Composite (MSFC), MS Quality of Life-54, and cranial MRI over 6 months. Overall quality of life (OQOL) correlated highly with emotional well-being, the mental health composite, health distress, and the physical health composite. In contrast, there was no statistical evidence of consistent correlation between OQOL and EDSS, MSFC, or MR outcome measures.