Multiple sclerosis and fibromyalgia syndrome may spur substantial disability for those affected. Using structural equation modeling, this secondary analysis examined predictors of disability in women with multiple sclerosis (n = 118) and fibromyalgia syndrome (n = 197) recruited for separate wellness studies. Greater functional limitations, lower economic adequacy, less social support, and higher depressive symptoms predicted greater disability in both groups. The final multigroup model showed good fit [chi][superscript 2] [(111, n = 315) = 135.92, comparative fit index = 0.99, root mean square error of approximation = 0.03] and identified similarities and differences across groups.