Using Engel’s (1977, 1980) biopsychosocial model and family systems theory, this study explored the associations between MS patient and partner reports of physical functioning, depression, and couple relationship quality. The hypothesis of this study stated that depression scores would be negatively related to and couple relationship quality scores positively related to MS patient physical functioning. Method. Fifty-four couples recruited from the MS society completed written self-report questionnaires about couple relationship quality (DAS [Spanier, 1976]), depression (CES-D [Radloff, 1977]), demographic data, and physical functioning (ADLMS [Gulick, 2003]). Results. In regression analyses, couple relationship quality positively related to MS patient physical functioning based on DAS reports by MS patients and partners. Depression negatively related to MS patient physical functioning according to MS patient and partner reports. Both MS patient and partner reports of couple relationship quality negatively related to depression scores in partners. While MS patient reports of couple relationship quality negatively related to MS patient depressions scores, partner reports of couple relationship quality were not significantly related. Conclusions. Depression and couple relationship quality were associated with MS patient physical functioning, though no causal pathways can be drawn from the present research. Couple relationship quality also relates to depression and couples with higher relationship quality may be better able to cope with the stresses of MS and avoid some of the emotional and psychological distress related to greater MS symptom exacerbation. Thus, clinicians and healthcare providers need to include partners in MS patient treatment. Finally, further research is needed to better explain causality between MS patient physical functioning, depression, and couple relationship quality.