Introduction Autoimmune hemolytic anemia occurs due to the accelerated destruction of erythrocytes as a result of the dysfunction of immune system cells, which produce antibodies against the normal antigens of the membrane of hematopoietic cells. One of its causes is systemic lupus erythematosus. Materials and methods We present a case of a 20-year-old patient who was hospitalized with acute autoimmune hemolytic anemia, having been diagnosed with SLE at the age of 18 years. At the onset of the disease, hemolytic anemia was a differential diagnostic challenge. Results The differential diagnosis between primary and secondary autoimmune hemolytic anemia (AIHA) was an important step. The presence of antinuclear antibodies (ANA Hep2, Anti-dsDNA, Anti-cardiolipin, Anti-phospholipids, anti-Ro, Anti-Sm B) were important arguments in making the diagnosis. The relapse of AIHA was caused by inadequate treatment, due to a lack of compliance. Pulse therapy combined with methylprednisolone and cyclophosphamide successfully resolved the AIHA. Conclusions Hematological abnormalities are commonly seen in SLE patients, but hemolytic autoimmune anemia is a rare condition. A timely diagnosis of the cause of hemolytic anemia and proper treatment of lupus by correcting autoimmune disorders are crucial in disease management. Pulse therapy combined with corticosteroids and immunosuppressants is effective in acute relapses of hemolytic anemia.