Cardiovascular (CV) morbidity is the major cause of death in patients with Systemic Lupus Erythematosus (SLE). Previous studies on mannose-binding lectin (MBL) gene polymorphisms in SLE patients suggest that low levels of complement MBL are associated with cardiovascular disease (CVD). However, as large studies on MBL deficiency based on resulting MBL plasma concentrations are lacking, the aim of our study was to analyze the association of MBL concentrations with CVD in SLE patients. Plasma MBL levels SLE patients included in the Swiss SLE Cohort Study were quantified by ELISA. Five different CV organ manifestations were documented. Of 373 included patients (85.5% female) 62 patients had at least one CV manifestation. Patients with MBL deficiency (levels below 500 ng/ml or 1000 ng/ml) had no significantly increased frequency of CVD (19.4% vs. 15.2%, P = 0.3 or 17.7% vs. 15.7%, P = 0.7). After adjustment for traditional CV risk factors, MBL levels and positive antiphospholipid serology (APL+) a significant association of CVD with age, hypertension, disease duration and APL+ was demonstrated. In our study of a large cohort of patients with SLE, we could not confirm previous studies suggesting MBL deficiency to be associated with an increased risk for CVD.