BACKGROUND The immunoregulatory role of vitamin D has been the object of a growing number of studies in patients with systemic lupus erythematosus (SLE). OBJECTIVE To determine the serum levels of 25-hydroxyvitamin D3 [25(OH) D] in patients with SLE, and to assess the association of 25(OH)D insufficiency/deficiency with clinical parameters and laboratory tests. METHODS Cross-sectional, prospective study performed at the SLE Clinic, Department of Rheumatology, Hospital das Clínicas, Universidade Federal de Pernambuco with convenience sampling, including 78 patients with SLE and 64 volunteers (comparison group), matched by gender and age. RESULTS Insufficiency/deficiency of 25(OH)D was found in 45 (57.7%) patients with SLE and 25 (39%) individuals in the comparison group. The mean serum levels of 25(OH)D were 29.3 ng/mL (6.1-55.2 ng/mL) in patients with SLE and 33.12 ng/mL (15.9-63.8 ng/mL) in the comparison group, and this difference was statistically significant (P = 0.041). No statistically significant difference was observed between the mean ages of both groups. No statistically significant association was observed between 25(OH)D insufficiency/deficiency and the following: time to diagnosis; disease activity (SLEDAI > 6); fatigue; use of corticosteroids and antimalarials; and anti-DNA. CONCLUSIONS High prevalence of 25(OH)D insufficiency/deficiency was found in patients with SLE (57.7%), with statistically significant difference as compared with the comparison group. No association of vitamin D insufficiency/deficiency was observed with the clinical variables and laboratory tests studied. The authors emphasize the importance of determining 25(OH)D serum levels in all patients with SLE, regardless of where they live and time to disease diagnosis.