Our objective was to compare patients with concurrent and sequentially presented systemic lupus erythematosus (SLE)-related protein-losing enteropathy (PLE). Patients with history of SLE admitted for PLE were selected and their clinical, laboratory, endoscopic and imaging characteristics, treatment and outcome were analyzed. From 2001 to 2010, 21 and 27 patients had concurrent and sequentially presented SLE-related PLE, respectively, and their clinical characteristics were comparable except the following: the concurrent group had more pleural effusion (P < 0.01), cutaneous (P < 0.03), neurological (P = 0.02) manifestations, higher creatine phosphokinase (127.6 IU/L vs. 105.7 IU/L, P < 0.05) and lactate dehydrogenase (504.0 IU/L vs. 422.2 IU/L, P < 0.05); whereas the sequential group had higher anti-double strand DNA titer (179.8 vs. 100.4, P < 0.05), 24-h urine protein excretion (1.1 g/d vs. 0.6 g/d, P < 0.05) and increased proteinuria after onset of PLE (0.21 g/d vs. 1.1 g/d, P < 0.04). The endoscopic, histological and radiological features were comparable between the two groups. More patients from the sequential group required more potent immunosuppressive therapy for induction (55.6% vs. 14.3%, P = 0.002) and maintenance (48.2% vs. 9.5%, P < 0.01).The concurrent group associated with better treatment outcomes, with requiring shorter mean time (4.5 months vs. 7.9 months, P = 0.03) for normalbuminemia and more individuals (90.5% vs. 63%, P < 0.02) achieving normalbuminemia in first year. The complications were infrequent: two drug-related adverse events from each group, one patient each from the concurrent group developed shingle and SLE nephropathy. PLE associated with concurrent and sequentially presented of SLE are comparable in clinical behavior; and the immunosuppressive therapy is generally well-responded and tolerated. However, the concurrent group is associated with better disease activity control.