Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune illness with an unknown cause. Autoantibody generation and probable involvement of practically every organ are hallmarks of SLE. There have been reports of significant regional variations in SLE prevalence. This difference is probably brought on by a number of sociodemographic factors, including ethnicity, geography, social support, medication compliance, environmental and occupational factors, as well as race and ethnicity. SLE generally affects women more frequently than it does men. But the severity of a disease is significantly impacted by gender difference. Objective: The study's goals were to look at the impact of age at onset and gender on illness features. Patients and methods: This was aprospective cross-sectional study carried out in Assiut University Hospital, Internal Medicine Department, registered in Clinical trial.gov: NCT04234633. SLE diagnosed based on criteria were recruited. Results: Our study included 185 patients, 75 were males and 110 were females. It revealed that there was statistically significant increase in alopecia and arthritis in the female group while increased incidence of nephritis and thrombocytopenia in the male group. Also, male patients have higher Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC DI) compared to females. On the other hand, there was no difference between the two groups regarding other manifestations of SLE, serological markers or severity indices. Conclusion: We concluded that gender could influence the clinical picture of SLE and the outcome.