Systemic lupus erythematosus (SLE) is uncommon in young children and unusual in infancy. Although a variety of liver pathologies have been reported in SLE, presentation of this disease with granulomatous liver involvement is very rare. In this article, for the first time, we report an infant girl presenting with unexplained hepatosplenomegaly and non-necrotizing granulomatous liver involvement at the age of six months who later developed pancytopenia and proteinuria and was finally diagnosed with SLE at the age of three years. Therefore, we suggest that SLE could be considered as one of the possible differential diagnoses when infants or children present with unexplained granulomatous liver involvement.