ObjectivesTo assess the reliability and validity of two disease-specific questionnaires that assess the quality of life (QoL) among patients with Systemic Lupus Erythematosus (SLE); SLEQoL and LupusQoL in Malay language. This study also identified the factors affecting each domain of the questionnaires.MethodsThis cross-sectional study was conducted from June 2021 until April 2022, and SLE patients were recruited to complete the SLEQoL, LupusQoL and Short Form Health Survey (SF-36) in Malay language. Disease activity were recorded using the modified SLE Disease Activity Index (M- SLEDAI) and British Isles Lupus Assessment Group 2004 (BILAG-2004) index. Presence of organ damage was determined using the SLICC Damage index. Cronbach’s alpha was calculated to determine internal consistency while exploratory factor analysis was done to determine the construct validity. Concurrent validity was evaluated using correlation with SF-36. Multiple linear regression analysis was deployed to determine the factors affecting each domain of SLEQoL and LupusQoL.ResultsA total of 125 subjects were recruited. The Cronbach’s α value for the Malay-SLEQoL (M-SLEQoL) and Malay-LupusQOL (M-LupusQoL) was 0.890 and 0.944 respectively. Exploratory factor analysis found formation of similar number of components with the original version of questionnaires and all items have good factor loading of >0.4. Both instruments also had good concurrent validity with SF-36. M-SLEQoL had good correlations with BILAG-2004 and M-SLEDAI scores. Musculoskeletal (MSK) involvement was independently associated with lower M-SLEQoL in physical function, activity and symptom domains. Meanwhile, MSK and NPSLE were associated with fatigue in M-LupusQoL.ConclusionBoth M-SLEQoL and M-LupusQoL are reliable and valid as disease -specific QoL instruments for Malaysian patients. The M-Lupus QoL has better discriminative validity compared to the M-SLEQoL. SLE patients with MSK involvement are at risk of poor QoL in multiple domains including physical function, activity, symptoms and fatigue.