Systemic lupus erythematosus (SLE) has been associated with atherosclerotic cardiovascular disease (CV) and an altered lipid profile. High levels of apolipoprotein C-III (ApoC3) are associated with elevated triglyceride levels and an increased risk of CV. In the present study, we aimed to study circulating ApoC3 in patients with SLE and describe its relationship with the manifestations of the disease. This is a cross-sectional study that included 186 patients with SLE. Disease-related data, CV comorbidity, full lipid profile, and serum levels of ApoC3 were assessed. A multivariable regression analysis was performed to study how ApoC3 was related to SLE features. Classic CV risk factors were significantly and strongly associated with circulating ApoC3. After a fully multivariable analysis that included classic CV risk factors and lipid profile molecules, SLICC damage (beta coef. 0.10 95% CI 0.02-0.19 mg/dl, 0.020) and Katz severity (beta coef. 0.11 95% CI 0.03-0.19 mg/dl, p = 0.011) indices and SLEDAI activity score (beta coef. 0.05 95% CI 0.05-0.08 mg/dl, p = 0.004) were all independently associated with higher levels of circulating ApoC3. Among SLE patients, disease activity, severity, and disease damage are independently associated with higher ApoC3 serum levels.