Serum levels of C-reactive protein (CRP) often remain low despite high disease activity in systemic lupus erythematosus (SLE). Sera from 96 patients with renal biopsy-proven active lupus nephritis, 24 of 96 patients in remission, and 49 patients with SLE with negative urinalysis (nonrenal SLE) was collected. Immunoglobulin G autoantibodies against monomeric CRP (mCRP) were screened by enzyme-linked immunosorbent assay with purified human CRP. Associations with clinical features, pathological data, and laboratory findings were investigated. The prevalence of mCRP autoantibodies in active lupus nephritis (57/96, 59.4%) was significantly higher than that in patients with SLE without clinical evidence of kidney involvement (20/49, 40.8%, p = 0.034). For the 13 patients with positive mCRP autoantibodies and sequential sera, their positive mCRP autoantibodies in active phase turned negative in remission (13/13, 100%). Patients with mCRP autoantibodies had significantly higher SLEDAI scores than patients without mCRP autoantibodies (18.3 +/- 5.2 vs 15.8 +/- 4.0, p = 0.013), who were more likely to experience acute renal failure (14/55 vs 2/33, p = 0.022), oral ulcer (15/57 vs 3/39, p = 0.022), and delayed activated partial thromboplastin time (18/52 vs 2/38, p = 0.001). Positive correlations between levels of mCRP autoantibodies and semiquantitative scores of renal histologic features were first observed in lupus nephritis as follows: interstitial inflammation (r = 0.328), tubular atrophy(r = 0.276), interstitial fibrosis (r = 0.211), and chronicity index score (r = 0.243). Autoantibodies against mCRP are prevalent in patients with lupus nephritis and are associated with disease activity and renal tubulointerstitial lesions.