Associating systemic lupus erythematosus (SLE), with an initial presentation of hemolytic uremic syndrome (HUS) is rare. We report a case of 21-year old Afghani female admitted to our hospital with an initial complaint of high grade fever and diffuse maculopapular rash and swelling of lower limbs. Diagnosis of atypical HUS was established according to the clinical triad of HUS without a veriotoxin-producing organism in her stool and the pathological finding compatible to thrombotic microangiopathy. In addition, her symptoms fulfilled the 1982 revised criteria for the classification of SLE. After pulse methylprednisolone, cyclophosphamide and plasmapheresis therapies, her laboratory findings and general condition improved. Unfortunately she was lost to follow up as she decided to return back to Afghanistan.