Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease which can affect various tissues and organs, posing significant challenges for clinical diagnosis and treatment. The etiology of SLE is highly complex with contributions from environmental factors, stochastic factors as well as genetic susceptibility. The current criteria for diagnosing SLE is based primarily on a combination of clinical presentations and traditional lab testing. However, these tests have suboptimal sensitivity and specificity. They are unable to indicate disease cause or guide physicians in decision-making for treatment. Therefore, there is an urgent need to develop a more accurate and robust tool for effective clinical management and drug development in lupus patients. It is fortunate that the emerging Omics have empowered scientists in the discovery and identification of potential novel biomarkers of SLE, especially the markers from blood, urine, cerebrospinal fluids (CSF), and other bodily fluids. However, many of these markers have not been carefully validated for clinical use. In addition, it is apparent that individual biomarkers lack sensitivity or specificity. This review summarizes the sensitivity, specificity and diagnostic value of emerging biomarkers from recent studies, and discusses the potential of these markers in the development of biomarker panel based diagnostics or disease monitoring system in SLE.