Titers of serum anti-double-stranded DNA antibodies (anti-dsDNA Abs) and C3 and C4 are used for monitoring systematic lupus erythematosus (SLE) patients. Here, we assessed the relationship between the clinical activity index (SLEDAI) and serum titers of anti-dsDNA Abs, C3, and C4 in an 8-year prospective study conducted in 194 SLE patients. The association of anti-dsDNA Abs and complement with M-SLEDAI was significant but low. Ninety-eight of the 194 patients were selected because they were followed for at least 5 years. We observed four types of clinical-serological patterns: parallelism between serum and clinical activity (n = 24), clinical quiescence with partial serum activity (n = 30), clinical quiescence but serologically fully active (n = 18), and clinical activity but serologically quiescent (n = 21). The serological markers evaluated are of limited utility in the monitoring of SLE patients and their use must be individualized.