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Systemic lupus erythematosus (SLE) in males is rare and poorly understood. Thus, still little is known about sex differences in SLE. We set out to identify sex differences regarding clinical manifestations as well as renal and cardiovascular outcomes of SLE. We analyzed patient data from the Swiss SLE Cohort Study. Cumulative clinical manifestations according to the updated American College of Rheumatology criteria were recorded at inclusion. Cardiovascular events were recorded within Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-SDI). Renal failure was defined as eGFR < 15 ml/min/1.73 m, initiation of renal replacement therapy or doubling of serum creatinine which were all assessed yearly or documented as end stage renal disease in SLICC-SDI. Risk differences were calculated using logistic regression and cox regression models. We analyzed 93 men and 529 women with a median follow up time of 2 years. Males were significantly older at diagnosis (44.4 versus 33.1 years, p < 0.001) and had less often arthritis (57% versus 74%, p = 0.001) and dermatological disorders (61% versus 76%, p < 0.01). In multivariate analysis female sex remained a significantly associated with arthritis and dermatological disorders. In multivariate analysis men had a significantly higher hazard ratio of 2.3 for renal failure (95% confidence interval (95%-CI) 1.1-5.2, p < 0.04). Total SLICC-SDI Score was comparable. Men had significantly more coronary artery disease (CAD) (17% versus 4%, p < 0.001) and myocardial infarction (10% versus 2%, p < 0.01). In multivariate analysis, male sex remained a significant risk factor for CAD (odds ratio (OR) 5.6, 95%-CI 2.3-13.7, p < 0.001) and myocardial infarction (OR 8.3, 95%-CI 2.1-32.6, p = 0.002). This first sex study in a western European population demonstrates significant sex differences in SLE. Male sex is a risk factor for cardiovascular events and renal failure in SLE. Potential etiological pathomechanisms such as hormonal or X-chromosomal factors remain to be further investigated.