Introduction: Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease that may involve the central nervous system, which is known as neuropsychiatric SLE. Both depressive and anxiety disorders have been reported as comorbidities of SLE, but the relationship remains controversial. Objectives: The aim of this study was to evaluate the risk of developing depressive and/or anxiety disorders in patients with SLE. We performed a matched case-control study using data from the Longitudinal Health Insurance Database 2000, 2005, and 2010 (LHID2000, LHID2005 and LHID2010, respectively), which are part of National Health Insurance Research Database (NHIRD). Study subjects were diagnosed as SLE during our study period (from the start of 2002 to the end of 2010), without psychiatric diagnoses before enrollment. Proportional hazard analyses with and without important covariates were applied to determine the relationship between SLE and depressive and/or anxiety disorders. Results: We identified 904 SLE patients and age-, gender-matched 4,520 controls in this study. We found a significantly increased risk of depressive and/or anxiety disorders (adjusted hazards ratio (HR): 1.79; 95% confidence interval (CI): 1.08-2.97). Conclusions: To our knowledge, this is one of the few studies reporting a significantly increased risk of depressive and/or anxiety disorders in patients with SLE after adjusting for important risk factors in a national healthcare database. The findings suggest SLE is a significant risk factor for the development of depressive and/or anxiety disorders. Further investigation on underlying mechanisms will be warranted.