Objective Anti-C-reactive protein (CRP) antibodies have been described in patients with systemic lupus erythematosus (SLE). We investigated the potential of the anti-CRP antibody as a marker for disease activity in SLE patients and as a predictor of progression to SLE in patients with incomplete lupus. Methods Immunoglobulin G anti-CRP antibody levels were measured using an enzyme-linked immunosorbent assay. Results Patients with incomplete lupus exhibited clinical and immunologic characteristics different from those in SLE patients: no serositis and alopecia, more common oral ulcers and arthritis, lower disease activity index, lower positivity for antinuclear and anti–double-strand DNA antibodies, and higher complement levels. Anti-CRP antibody levels were higher in SLE patients (35.6 [35.1] AU) than in patients with incomplete lupus (23.1 [25.8] AU, P = 0.016) and normal controls (21.0 [14.3] AU, P < 0.001). Anti-CRP antibody was significantly higher in SLE patients with arthritis and correlated with disease activity markers, including antichromatin antibody. However, no difference in anti-CRP antibody levels was observed between patients with incomplete lupus that progressed to SLE and those whose did not. Conclusion These data suggest that anti-CRP antibodies can neither be used as biomarkers in SLE nor predict SLE progression in patients with incomplete lupus.