Background: Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are systemic inflammatory diseases that are associated with increased risk of cardiovascular disease. Systemic inflammation in RA and SLE may contribute to accelerated atherogenesis through alteration of the plasma lipid profile. The aim of this study was to assess the relationship between disease activity and lipid levels in patients diagnosed with RA and SLE. Methods: This was a retrospective cohort analysis of patients diagnosed with SLE or RA at the King Abdul Aziz University Hospital, Saudi Arabia from August 2010 to August 2011. Demographic and biochemical data was extracted from medical records. Differences in the levels of total cholesterol (TC), high density lipoprotein (HDL)cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides (TG) between RA and SLE patients were analysed using chi square tests. Associations between lipid levels and disease activity were analysed using partial correlations. Results: 250 patients met the inclusion criteria and were included in the study population. 155 patients had been diagnosed with SLE and 135 with RA, of whom 41 had been diagnosed with both diseases. Patients diagnosed with both SLE and RA had lower mean ANA and RF titres compared to those diagnosed with a single disease (p<0.001 and p=0.040 respectively). CRP and ESR levels were similar in the three groups. Patients with an RA-only diagnosis had higher TG levels and lower HDL levels, whilst SLE patients had a significantly higher TC/HDL ratio. TC was negatively correlated with ANA (r=-0.161, p=0.046) and CRP (r=-0.176, p=0.01) and positively correlated with RF (r=0.191, p=0.028); TG was positively correlated with ESR (r=0.215, p=0.001) and CRP (r=0.139, p=0.043); LDL-C was negatively correlated with ESR (r=-0.199, p=0.026) and HDL-C was negatively correlated with ANA (r=-0.223, p=0.046 (Table 3). Conclusion: Higher concentrations of markers and mediators of inflammation and disease activity in patients with SLE and RA are associated with changes in lipid levels which may infer greater cardiovascular risk.