Nucleosomes and the broad family of antinucleosome antibodies (ANAs; anti-double-stranded DNA, antihistone and antinucleosome antibodies) may contribute to the pathogenesis of systemic lupus erythematosus (SLE). We collected clinical information on 90 patients with SLE and 73 healthy volunteers and measured serum levels of the ANA family using a double-sandwich ELISA. The results showed that the levels of serum nucleosomes of patients with SLE was significantly lower and the levels of ANA were significantly higher than healthy controls. Negative correlations between serum nucleosomes and ANA, and positive correlations between individual ANAs were found. Patients with SLE with positive ANA had a significantly higher frequency of renal disorders than those with negative ANA. Determination of serum nucleosomes and ANAs contributes to SLE monitoring.