Our objectives were to examine the prevalence of work disability (WD) and factors associated with job loss in systemic lupus erythematosus (SLE) in a large, multi-centered Canadian sample to determine the current prevalence of WD and identify the contribution of disease activity, damage, and co-morbidities with respect to WD in this cohort. Cross-sectional data on WD status from the 1000 Canadian Faces of Lupus database (a multi-center multi-ethnic cohort of SLE patients) along with clinical measures (number of ACR criteria ever, SLICC Damage Index, SLAM, SLEDAI, SF-36 and Charlson Co-morbidity Index scores), demographic features (age, sex, high school education, household income, marital status, disease duration, employment status) and co-morbidities (including self-reported fibromyalgia, arthralgias, depression and fatigue) were used in bivariate and logistic regression analyses. The 1137 SLE patients had a mean age of 50 years (SE 0.75) and mean disease duration was 18 years (SE 0.70); 19.09% were work disabled and 49.78% were employed. Those with WD were more likely than non-WD SLE patients to have: a higher number of ACR criteria for SLE; not completed high school; older age; single marital status; a lower household income; longer disease duration; higher SLICC Damage Index and SLAM scores; lower SF-36 PCS and SF-36 MCS scores; less vigorous activity per week; and fibromyalgia, arthralgias, fatigue and depression (p < 0.05). This contemporary rate of WD is lower than many past reports. Socio-demographic factors, co-morbidities (fibromyalgia and fatigue) and disease related factors were strongly associated with WD. We cannot determine cause and effect as the study was cross-sectional.