Systemic lupus erythematosus (SLE) and sickle cell disease (SCD) are relatively common disorders, the co-existence of these two conditions in an individual is rare. Because of the similarities of the musculoskeletal, central nervous system, and renal manifestations in both diseases, diagnosis of SLE in patients with SCD can be difficult to establish. Both SCD and sickle cell trait (SCT) can have a cumulative assault on the progression of chronic kidney disease (CKD). We report a case of a 23-year-old female from an endemic region of SCD in Nepal who presented initially with the symptoms of urinary tract infection (UTI) but later was found to have co-existent SCT and SLE. Ultrasonography of the abdomen and pelvis revealed Grade I medical-renal disease with increased echotexture of the kidney. High-Performance Liquid Chromatography (HPLC) was performed on the background of her ethnicity which was suggestive of sickle cell trait (HbS). A renal biopsy was performed which showed co-existing lesions of membranous lupus nephritis (class V) and focal lupus nephritis (class III) with no evidence of Sickle cell nephropathy was seen microscopically. She was managed with immunosuppressive medications. She is now in remission and kept on regular follow-up. The coexistence of both SCT and SLE in a single individual is rare. SCT and SLE can have multi-system manifestations with positive anti-nuclear antibodies (ANAs). The coexistence of both can accelerate the rate of kidney damage but it isn't always the same as in our case. This association is more relevant in our setting as sickle hemoglobinopathies are the most common in the Western Terai of Nepal.