Background Health-related quality of life (HRQOL) as a patient reported outcome plays important roles in the life of patients with RA (rheumatoid arthritis) and SLE (Systemic lupus erythematosus) as well as their families. Evaluating the impact of sustained remission on HRQOL is important and could be of potential help in daily practice. Thus, we aimed to assess and compare prospectively the impact of sustained remission on HRQOL in Saudi RA and SLE female cohorts. Results Sixty-two female patients with active RA and 34 female patients with active SLE fulfilled the inclusion-, entry- and follow-up criteria. At baseline, the SLE patients had significantly better SF-36 scores than the RA patients. In both groups, significant correlations were found between disease activity and physical (PCS) and mental (MCS) components summary of the SF-36 (all p’s ≤ 0.001). In sustained remission, both SLE and RA patients showed significant improvements of the SF-36 scores (p < 0.001) compared to baseline. RA patients in sustained remission had a significantly better general health, bodily pain and physical functioning, and total PCS scores (p < 0.001) than those with SLE. Conclusions Both SLE and RA patients in sustained remission showed strongly improved HRQOL. In sustained remission, RA patients had comparable or better HRQOL than SLE patients.