The objective of this study was to examine health-related quality of life (HRQOL) and social support in patients with systemic lupus erythematosus (SLE) and compare it with healthy people, to identify the relationship between social support and HRQOL in SLE patients, and to assess the influence of age, SLE Disease Activity Index (SLEDAI) and disease duration on HRQOL. We administered The Medical Outcomes Study Short Form-36 (MOS SF-36) questionnaire and the Social Support Rate Scale (SSRS) to a group of 202 patients with SLE and a healthy control group of 207 individuals. Spearman correlation was performed to identify the relationship between social support and HRQOL in SLE patients. The ordinal regression analyses were used to identify independent variables that were associated with the PCS and MCS. Results show that the physical (PCS) and mental (MCS) component summary scores of MOS SF-36 were lower in patients compared with healthy controls. Patients with SLE have a poorer social support as compared with healthy controls in subjective support, objective support, and availability of support. There was a positive correlation between social support and PCS and MCS. MCS and PCS were negatively associated with age and SLEDAI. MCS were negatively associated with disease duration. Taken together, this data suggested that patients with SLE have significant impairment of their HRQOL and less social support. HRQOL may be affected by social support, age, and SLEDAI.