Abstract: INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is a clinical condition with increased red cell destruction or decreased red cell survival due to autoantibodies against self-antigens on red blood cells. AIHA may be primary or secondary to other underlying illness. Systemic lupus erythematosus (SLE) is the most common secondary cause of AIHA. Although the incidence of AIHA in SLE patients is low (5%–10%), sometimes, it causes severe anemia which requires blood transfusion. Characterization of these autoantibodies in AIHA is very important, because the clinical condition and treatment of the patient depend on the optimal temperature reactivity, class, and subclass of immunoglobulin responsible. AIM AND OBJECTIVES: The aim and objective of this study are to perform detailed characterization of red cell autoantibodies for accurate diagnosis of AIHA in SLE patients, to find out specific class (immunoglobulin G [IgG]/IgM/IgA) of immunoglobulin and/or complement (C3c/C3d) responsible for AIHA, and their association with severity of hemolysis. MATERIALS AND METHODS: This was a prospective analytical study, done at a tertiary care hospital in Hyderabad, conducted between February 2021 and May 2022. SLE patients with AIHA were included in the study. Monospecific direct antiglobulin test (DAT) was performed to identify the specificity of autoantibody or complement. Based on hematological laboratory values, the study population was divided into three groups, i.e., mild, moderate, and severe hemolysis. DAT strength, hemolytic parameters, and severity of hemolysis were compared between different types of AIHA in SLE patients. Correlation statistics were used to know the association of severe hemolysis with DAT strength and different combinations of autoantibodies. RESULTS: Among 150 patients enrolled, 16 (10.6%) patients had severe hemolysis, 51 (34%) patients had moderate hemolysis, and 83 (55.3%) patients had mild hemolysis. Only IgG was positive in 109 (72.6%) patients, both IgG and C3d were positive in 37 (24.6%) patients, C3d was positive in 4 patients, and IgM was positive in 19 patients. High DAT reaction strength (3+–4+) and presence of C3d or IgM along with IgG were moderately correlated with severe hemolysis. CONCLUSION: Warm AIHA is the most common type of AIHA in SLE patients mediated by IgG. Mild and moderate hemolysis was seen in most cases. Severe hemolysis was moderately correlated with the presence of C3d or IgM. Further studies are warranted to find the predisposing factors leading to severe hemolysis.