Diagnosis of SLE is based on clinical manifestations and laboratory findings. Timely diagnosis and treatment are important to control disease activity and prevent organ damage. However, diagnosis is challenging because of the heterogeneity in clinical signs and symptoms, and also because the disease presents with alternating periods of flare and quiescence. As SLE is an autoimmune disease characterised by the formation of autoantibodies, diagnostic immunology laboratory tests for detecting and quantifying autoantibodies are commonly used for the diagnosis and classification of SLE. These include ANA, anti-double-stranded DNA antibodies and anti-Smith antibodies, together with other antibodies such as antiphospholipid or anti-Cq1. Complement proteins C3 and C4 are commonly measured in patients with SLE, but their serum levels do not necessarily reflect complement activation. Cell-bound complement activation products (CB-CAPs) are fragments formed upon complement activation that bind covalently to haematopoietic cells. This review focuses on the complement system and, in particular, on CB-CAPs as biomarkers for the diagnosis and monitoring of SLE, vis-à-vis complement proteins and other biomarkers of complement activation.