Objective: Cardiovascular (CV) morbidity is a well-established problem in systemic lupus erythematosus (SLE). Antimalarial (AM) therapy has been seen as a potential atheroprotective agent. The aim was to assess the impact of AM therapy on traditional and novel atherosclerosis (AT) biomarkers in patients with SLE. Methods: A search of MEDLINE, EMbase, and Cochrane library for studies evaluating the impact of AM on AT biomarkers in SLE was conducted. Data extraction included serum, functional and structural traditional and novel biomarkers. A narrative synthesis of the findings and a meta-analysis with random effects was conducted estimating mean differences (MD), OR, HR and 95% CIs. Results: The search strategy produced 148 articles, of which 64 were extracted for analysis. The MD in VLDL-cholesterol (-10.29, 95% CI -15.35, 5.24), triglycerides (-15.68, 95% CI -27.51, -3.86), and diastolic BP (-3.42, 95% CI -5.62, -1.23) differed significantly in patients on AM therapy compared with those without AM therapy. Patients on AM had a lower prevalence and incidence of diabetes mellitus than patients not on AM (HR: 0.39, 95% CI 0.17, 0.88). HCQ use was associated with lower blood pressure (BP) variability. Structural markers like carotid intima-media thickness (IMT), carotid plaque (CP) and coronary artery calcification (CAC) were not influenced by AM. For functional markers like endothelial and arterial stiffness the benefit was unclear. The GRADE approach showed a very low-to-low quality of evidence (QoE) per outcome. Conclusions: There is some evidence on the associations between AM therapy and some AT markers. However, the data on which this conclusion was based was of low to very low evidence.