Systemic lupus erythematosus (SLE), the prototype autoimmune disease, is characterized by the production of a plethora of autoantibodies with various roles in the development of diseaserelated tissue damage. C-reactive protein (CRP) is an acute phase reactant with a pentameric structure. Under acidic or alkaline conditions, or when urea levels are high and/or calcium levels are low, the pentamer (pCRP) dissociates irreversibly into monomeric CRP (mCRP) and exposes new epitopes (neo-CRP). Importantly, anti-mCRP (but not anti-pCRP) antibodies have been described in patients with SLE, their prevalence varying from 4% to 78% in different cohorts. Numerous studies have investigated the relationship between autoantibodies directed against CRP (anti-CRP) and disease activity as well as their association with lupus nephritis (LN), frequently reporting discrepant findings. The main objective of the present review is to describe the role of anti-mCRP antibodies in SLE according to the currently available data.