Objective. To examine the clinical correlates of thrombocytopenia and the value of thrombocytopenia as a predictor of disease activity, damage accrual, and mortality in patients with systemic lupus erythematosus (SLE). Methods. SLE patients participating in a longitudinal multiethnic cohort were studied. Thrombocytopenia was defined as a platelet count <100,000/mm3 at or before enrollment (baseline). Patients were categorized by the presence and absence of thrombocytopenia. The impact of thrombocytopenia as well as severe thrombocytopenia (platelet count <50,000/mm3) on disease activity, damage accrual, and mortality was examined by multivariable analyses. Results. A total of 616 patients were studied; 121 of the patients (20%) had thrombocytopenia, of whom 30 had severe thrombocytopenia. By univariable analyses, those with thrombocytopenia had more pulmonary, neurologic, renal, and hematologic involvement, worse disease activity and damage, and higher mortality rates. By multivariable analyses, thrombocytopenia was associated with higher disease activity over the disease course (P = 0.018), but not with the accrual of damage either at baseline (P = 0.543) or at the last visit (P = 0.086); however, severe thrombocytopenia was associated with damage accrual at the last visit (P = 0.020). When poverty was not included in the models, thrombocytopenia (<100,000/mm3 or <50,000/mm3) was strongly associated with mortality (P < 0.001 for each comparison); however, the level of significance decreased some when poverty was included in the models. Conclusion. Thrombocytopenia early in the course of SLE is indicative of more severe and active disease. Severe thrombocytopenia is an independent predictor of damage accrual at the last visit. Thrombocytopenia is also an independent predictor of mortality, albeit of a lesser magnitude than that predicted by poverty. Patients with thrombocytopenia need close monitoring for possible undesirable outcomes. © 2007, American College of Rheumatology.