Background: Patients with systemic lupus erythematosus (SLE) may require prolonged periods of corticosteroid therapy which lead to excessive weight gain and increased cardiovascular risk. Objective: To assess the utility of a low glycaemic index diet in patients with corticosteroid dependent SLE in achieving weight loss and improving glycaemic control. Design: A total of 23 women were enrolled in a 6 week study. All had mild, stable SLE, were receiving corticosteroids and had a body mass index > 25 kg/m2. Subjects were randomly assigned to a low glycaemic index (Low GI) diet or a calorie restricted (Low Cal) diet. The primary end point was weight loss. Secondary end points included tolerability of diet, bio-markers of cardiovascular risk, disease activity, fatigue and sleep quality. Results: Weight loss in both treatment groups was significant (mean ± SD: Low GI diet 3.9 ± 0.9 kg; Low Cal diet 2.4 ± 2.2 kg, p < 0.01 from baseline in each group). There were also significant improvements in waist and hip measurements. However, the difference in weight loss and waist and hip measurements between the two diet groups was not statistically significant. There was a statistically significant reduction in Fatigue Severity Scale in both diet groups, (p < 0.03). Both Low GI and Low Cal diets were well tolerated, resulting in no serious adverse effects or increase in disease activity. Conclusion: Significant weight loss is achievable over 6 weeks in a diet-specific trial in subjects with stable SLE, who are on low dose prednisolone. Both diets were equally tolerable, and did not cause flares in disease activity. Our results suggest that dietary manipulation may significantly improve fatigue in subjects with SLE.