Background: Cognitive impairment among patients with systemic lupus erythematosus (SLE) can significantly impact quality of life (QoL). This study aimed to determine the prevalence of cognitive impairment in SLE patients using the Montreal Cognitive Assessment Indonesian version (MoCA-INA) and to assess its association with QoL. Methods: This was a cross-sectional study of SLE patients from the outpatient clinic at Cipto Mangunkusumo Hospital, Jakarta. Data collected included patient characteristics, MoCA-INA scores, the LupusQoL questionnaire, and the Hospital Anxiety and Depression Scale (HADS) scores. The independent T-test or Mann-Whitney U test was used to analyze the association between categorical independent variables and LupusQoL, while Spearman or Pearson correlation tests were used to examine the association between numerical independent variables and QoL. Other factors potentially associated with QoL — including disease duration, age, education level, comorbidities, disease activity, organ involvement, steroid dose, immunosuppressant medication, anxiety, and depression — were also assessed. A p-value < 0.05 was considered statistically significant. Results: Of the 116 subjects, 112 (96.6%) were female, with a mean age of 34.41 (± 10.15) years. Most participants had completed secondary education, were receiving corticosteroids, and had been prescribed hydroxychloroquine. The median MEX-SLEDAI score was 2.75 (range 0–6), and the most common organ involvements were mucocutaneous (90.5%) and musculoskeletal (91.4%) manifestations. The prevalence of cognitive impairment in SLE patients was 57.8%, with most patients experiencing mild cognitive impairment (98.5%). There was no significant difference in QoL between SLE patients with and without cognitive impairment (p = 0.750). Disease duration (r = 0.24, p = 0.011), anxiety (p < 0.001), and depression (p = 0.003) were significantly associated with QoL among SLE patients. Conclusions: More than half of the subjects experienced cognitive impairment. However, there was no significant difference in QoL between SLE patients with and without cognitive impairment. Clinical trial number: Not applicable. © The Author(s) 2025.