Disease specific measures like systemic lupus erythematosus (SLE) Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics (SLICC) and Systemic Lupus Activity Measure (SLAM) are primarily based on physician assessment of disease severity along with blood tests pertinent to SLE. These are primarily used for research purposes and do not quantify the social impact of the disease or measure function and well being from the patients perspective. We wish to study the degree of correlation between the SLEDAI, SLICC and patient reported health related quality of life (HRQOL), to see if these measures can be used to gauge the disease impact from the patient's perspective. The aim of the study was, therefore, to assess the correlation between SLICC, SLEDAI and HRQOL in patients with systemic lupus erythematosus. We utilized the University of Chicago SLE database to obtain SLEDAI, SLICC and MOS SF-36 scores. A physician not directly involved in their care assessed SLEDAI, SLICC and SF-36 at the same visit. STATA-7SE software was used to obtain the two summary scores [physical component summary (PCS) and mental component summary (MCS)]. Multiple linear regression and correlation coefficients were obtained to assess the direction and relationship between HRQOL and these disease specific measures. On multivariate regression models, both SLICC and SLEDAI were predictive of the PCS scores (beta SLICC = - 1.036, P = 0.025, 95% CI - 1.9, -0.13: beta SLEDAI = - 0.322, P = 0.012, 95% CI -0.57, -0.07. R2= 0.14). Neither SLICC nor SLEDAI were predictive of MCS scores (beta SLICC =-0.015, P=0.97, 95% CI -1.03, 1.001: beta SLEDAI=-0.19, P=0.174, 95% CI -0.47, 0.08. R2 = 0.02). The correlation coefficients between SLEDAI and PCS, MCS were -0.29 and -0.15, respectively. The correlation coefficients between SLICC and PCS, MCS were -0.27 and -0.02, respectively. The conclusions are that SLEDAI and SLICC are poor indicators of HRQOL of patients with SLE.