Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)>2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)>4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6 ± 7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p=0.003) and lupus anticoagulant (11.3% vs. 29.0%, p=0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7 ± 369 vs. 30.9 ± 17.3 GPI, p=0.02) and aCL IgM antibody levels (75.3 ± 357.4 vs. 9.3 ± 10.3 GPI, p=0.02), and marginally lower aCL IgG antibody levels (9.2 ± 4.9 vs. 9.7 ± 3.9 GPI, p = 0.096). While the ECLAM score significantly correlated with hyperferritinemia (p=0.04), the SLEDAI score was marginally associated with hyperferritinemia (p = 0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.