Background: Cardiovascular diseases (CVDs) are major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients. Resistin is an inflammatory adipocytokine associated with insulin resistance and an increased risk of CVD. Aim of the work: To study the possible role of resistin (RETN) +299A>G and +62G˃A gene polymorphisms in the development of CVDs among Egyptian SLE patients and their impact on cardio metabolic risk and disease activity. Patients and methods: +299A>G and +62G˃A genes polymorphisms were assessed in 140 patients and 100 controls by polymerase chain reaction (PCR). The carotid intima-media thickness (CIMT) was measured. SLE disease activity index (SLEDAI) was assessed. Serum resistin, homeostasis model assessments (HOMA-IR and HOMA-b), fibrinogen and homocysteine were measured. Results: The mean age of patients was 31.1 ± 7.6 years and disease duration 5.4 ± 2.5 years. Serum resistin was significantly increased in patients (4.9 ± 0.2 ng/ml) compared to control (3.02 ± 0.9 ng/ml) (p < 0.001). Serum resistin significantly correlated with uric acid (p < 0.001), homocysteine (p < 0.001), fibrinogen (<0.001) and SLEDAI (p < 0.001). AA genotypes and A allele +299G>A were significantly higher in patients than control (37.9% vs 10% and 63.6% vs 33.5%; p < 0.001). Serum resistin, CIMT, uric acid, fibrinogen and homocysteine was significantly higher in +299G>A GA and AA patients compared to GG (p < 0.001) and HOMA-b decreased (p < 0.001). HOMA-b, fibrinogen and uric acid were independently correlated with resistin (p < 0.001). Conclusion: Resistin +299G/A gene polymorphisms especially the AA genotype and A allele may play an important role in pathogenesis and activity of SLE as well as susceptibility to develop CVD in Egyptian population.