Background: Systemic Lupus Erythematosus (SLE) predominantly affects young females who are in their most productive years of life. SLE can cause organ damage and affects daily functioning and quality of life, causing work disability (WD). Methods: We developed a longitudinal study with 110 SLE patients, whose data were collected through individual standardized interview and review of medical records. We aimed to determine the prevalence of WD and its possible associated risk factors (sociodemographic, lifestyle habits, quality of life, clinical characteristic, cumulative organ damage and disease activity). To identify variables associated with work disability, two different multivariate regression models using a stepwise backward method were performed. Results: The percentage of WD due to SLE was 76.3%. An association was found between WD and lack of physical exercise (p=0.017) and high physical work demand (p=0.037). Clinical characteristics were not significant predictors of work dysfunction. Conclusion: 76.3% of our sample developed WD after SLE diagnosis. Participants who did not practice physical exercise and those who had a high-demand physical work were, respectively, 3.78 and 4.80 times more likely to have WD. Although we were not able to analyze the influence of COVID-19 in WD development, COVID-19 pandemic could have exacerbated the inequalities among people with chronic health conditions, especially in a low-income population, which could have influenced our results. Additional researches to evaluate risk factors for WD in low-income SLE patients and on strategies for reducing its impact are needed.