© The Author(s), 2016. Objective The objective of this paper is to compare disease activity and clinical features at diagnosis in male and female patients with systemic lupus erythematosus (SLE). Methods This was a cross-sectional study in which every male patient (n = 40) was matched with three female patients of the same age (±5 years) and racial/ethnic group; disease activity as per the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and disease manifestations at the time of diagnosis were compared. Results Alopecia and anti-Ro antibodies were more frequent in female patients. No statistically significant difference in any other disease characteristics was found. However, male gender was associated with a risk of severe disease activity at the time of diagnosis (as determined by SLEDAI ≥12 score) independent of age, racial/ethnic group, anti-Ro positivity or time to criteria accrual (OR: 3.11 95% CI, 1.09-8.92; p = 0.035). Conclusion In newly diagnosed SLE patients, male gender is associated with higher disease activity despite the fact that male and female patients seem to experience similar overall disease manifestations.