Abstract Objectives The aim of this national population-based, retrospective database study is to compare the comorbidity profiles of systemic lupus erythematosus (SLE) patients and general population controls matched for age, gender, and region and assess the risk of depression or anxiety when controlled for age, gender and adjusted for the Charlson Comorbidity Index (CCI). Methods Claims data of 1051 patients diagnosed with SLE (full population between January 01, 2011, and December 31, 2014) from the Hungarian National Health Insurance Fund have been analyzed against matched controls (1:5 ratio) with a follow-up of 30 months. The first record of SLE diagnosis was considered the diagnosis date. The odds ratio (OR) and 99.9% confidence interval (CI) of having depression or anxiety among patients with SLE vs. controls have been assessed using logistic regression models. Results SLE patients report more comorbidities than the matched general population both in pre- and post-index periods (mean CCI 1.79 vs. 1.15 and 2.78 vs. 1.22 [both p