Background: Systemic lupus erythematosus (SLE) is an important cause of secondary warm-antibody autoimmune hemolytic anemia (AIHA). The prevalence of AIHA has been estimated to range from 5% to 30%, but severe AIHA is comparatively less frequent in SLE patients. The severity of AIHA has rarely been studied in SLE patients;1–3 we thus have examined the predictors of severe AIHA using the extensive database of a large Latin American inception cohort. Methods: In patients with a recent diagnosis of SLE (≤ 2 years), factors associated with the occurrence of severe AIHA (hemoglobin level <7 g/dl) were examined by Cox proportional univariable and multivariable hazards regression analyses. Results: Of 1,349 patients, 103 (7.6%) developed AIHA over 5.4 (3.8) years. Of them, 49 (47.6%) patients were classified as having severe AIHA (Mestizos 44.9%, Caucasians 40.8%, and African-Latin American 14.3%). The median time from the first clinical SLE manifestation to the occurrence of severe AIHA was 3.7 months (IQR 1.4–15). In the univariable analyses, male sex and disease activity at diagnosis were associated with a shorter time to severe AIHA occurrence while malar rash and photosensitivity were associated with a longer time. By multivariable analysis and after adjusting for age at SLE diagnosis, gender, and ethnicity, male sex, and higher disease activity at diagnosis remained associated with a shorter time to the occurrence of severe AIHA. The results are shown in the Table below. Conclusions: Severe AIHA occurred in 3.6% of our cohort and it is an early manifestation of lupus. In Latin American patients with SLE, male sex represents more than a two-fold higher risk of experiencing severe AIHA at a faster pace. A higher level of disease activity at SLE diagnosis is also an independent predictor of the occurrence of severe AIHA in a shorter time.