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The objective of this study was to compare the clinical and immunological presentation of SLE between males and females in a Colombian SLE population. A cross-sectional, retrospective study was performed that evaluated patients with SLE over 6 years. The dependent variables were systemic complications, duration of hospitalization, readmission, and death. Descriptive, group comparison, bivariate, and multivariate analysis were performed using Stata 12.0 software 200 patients were included in this study, 84.5% were females and 15.5% males. Longer hospitalizations, readmissions, respiratory compromise, higher activity disease (ECLAM score), smoking, and use of cyclophosphamide in the past 3 months were more prevalent in males. In the bivariate and multivariate analysis, we found an increased risk in males of respiratory symptoms (OR 3.35), anti-DNA antibody (OR 2.46), smoking (OR 4.2), cyclophosphamide use (OR 3.23), chronic pulmonary alterations (OR 2.51), readmission (OR 2.88), long hospitalization (OR 3.12), and death (OR: 3.31). This is the first study that shows the differences related to gender in Colombian SLE patients. Males with SLE have more disease activity compare with females. Also, we found that males have more risk of pulmonary impairment, longer hospitalizations, hospital readmissions, and deaths.