The association of Klinefelter’s syndrome and systemic lupus erythematosus (SLE) is very rare, with about 21 cases described to date. We report on a patient who has developed pericarditis, arthritis, anemia and alopecia, while he has been using testosterone irregularly; the subnormal testosterone levels were coincident with the initial symptoms and re-incidences of SLE. This case is in agreement with the literature, which gives support to the hypothesis that sexual steroids participate in the emergence of autoimmune diseases, specially SLE.