Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). Tumour necrosisfactor-a (TNF-α) has been implicatedin the pathophysiologicalprocessesof both SLE and CVD. This study focuses on the role of TNF-α and its soluble receptors in SLE-related CVD. In summary, 26 women (52 + 8.2 years) with SLE and a history of CVD (SLE cases)were compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched population-based control women (population controls). Plasma concentrations of circulating TNF-α, TNF-α receptor 1 (sTNFR1) and TNF-α receptor 2 (sTNFR2) were determined by ELISA. TNF-α, sTNFR1 and sTNFR2 were raised in SLE cases as compared to SLE controls ( P = 0.009; P = 0.001; P = 0.001, respectively), and SLE controls had higher levels than population controls ( P = 0.001; P = 0.02; P = 0.001, respectively). Exclusively in the SLE case group there was a striking positivecorrelationbetweenTNF-α and plasma triglycerides( r = 0.57, P < 0.002), VLDL triglycerides ( r = 0.54, P = 0.004) and VLDL cholesterol ( r = 0.58, P = 0.002). Furthermore, TNF-α correlated with the waist-hip ratio but not with estimated insulin resistance. TNF-α may thus be a major factor in SLE-related CVD acting both by contributing to hypertriglyceridaemia and by promoting atherosclerosis-relatedinflammation. sTNFR1 and sTNFR2 are strongly associated with CVD in SLE but their exact roles in disease development remain to be elucidated.