Childhood-onset systemic lupus erythematosus (cSLE) is a systemic autoimmune disease characterized by the presence of autoantibodies. cSLE often affects multiple organs in the body and is known to have a poorer prognosis than adult-onset disease (Azevedo et al. 2014). Current laboratory tests are clearly insufficient for identifying and monitoring the disease. Recent studies have yielded novel biomarkers for cSLE which can be used for monitoring disease activity and response to treatment. The most encouraging biomarkers will be discussed herein and include cell-bound complement activation products, some genomic profiles, and urinary proteins such as neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and others. Previous studies suggested that a combination of the novel biomarkers might help to enhance sensitivity and specificity for early diagnosis, disease monitoring, and prediction of cSLE flares.