Psychiatric diagnosis in patients with systemic lupus erythematosus (SLE) is controversial: variations have been reported in frequency, diagnostic assays, associations with disease activity, autoantibodies, and contributing social factors. Eighty-three consecutive non-selected Chilean patients with SLE were evaluated for: (i) 26 common mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), using the Mini-International Neuropsychiatric Interview (MINI-plus); (ii) psychological suffering measured by Hospital Anxiety and Depression Scale (HADS); (iii) ACR 1999 neuropsychiatric (NP)SLE criteria; (iv) SLE disease activity (SLEDAI-2K); (v) cumulative damage (SLICC/ACR); and (vi) anti-ribosomal P antibodies by enzyme-linked immunoassay and immunoblot. Psychiatric diagnoses occurred in 44.6% of patients; the most frequent (21.7%) was major depressive episode (MDE). No association with lupus activity was observed in patients with a DSM-IV diagnosis or MDE or psychological suffering. ACR 1999 NPSLE criteria were present in 42.2% of patients, the majority corresponding to mood (28.9%) or anxiety disorders (15.6%). Suicidal risk was present in 9.6% of patients. Anti-ribosomal P antibodies (13.3%) were not associated with DSM-IV diagnosis. Severe psychiatric disorders in SLE are common and not associated with disease activity.