This study aimed to assess mental health status (depression, anxiety, and stress) and explore factors associated with the disease-specific quality of life among Systemic Lupus Erythematosus (SLE) patients in Thailand.This cross-sectional study used an online convenience sampling of 650 SLE patients who were registered members of the Thailand SLE Club. The study survey comprised of demographic information, health history, Depression, Anxiety, Stress Scale (DASS), and Lupus Quality of Life Scale (LupusQoL).The survey response rate was 61.2%. Out of 344 respondents, most were female (96.9%). The scores were suggestive of the presence of mild depression and stress, but moderate anxiety. The higher depression, anxiety, and stress levels were associated with lower education and income (r =  - .14 to - .29, p < .01) and higher number of SLE symptoms (r = .17 to .33, p < .05). Better quality of life was significantly related to lower number of symptoms, lower levels of stress/anxiety/depression, higher education, and better income. Also, the longer the patients were kept out of the hospital (last hospitalization), the better their quality of life. By using hierarchical multiple regression, four predictors of the quality of life were identified; the number of symptoms, stress, anxiety, and depression. These predictors combined explained 51% of the variance, F(5,108) = 24.34, p < .001, adjusted R = .51.To improve the quality of life, SLE patients should focus on self-management of their symptoms. Health care providers should include SLE self-care health education in the plan of care. They also should use multidisciplinary approach in order to provide holistic treatment, including psychological care.