The objective of this study was to identify the effects of mycophenolate mofetil (MMF) on non-renal manifestations in systemic lupus erythematosus (SLE). The study population comprised 439 SLE patients from the Korean Lupus Network registry who were followed up annually and completed the baseline survey and two follow-up visits from 2014 to 2018. Disease activity, laboratory markers, and clinical manifestations including mucocutaneous lesions, arthritis, serositis, neurological disorders, and hematologic/immunologic abnormalities were assessed. All variables by group (MMF and non-MMF) effects with time (baseline, 1st follow-up, and 2nd follow-up) were analyzed by generalized estimation equation. Seventy-two patients were treated with MMF. There was significant difference in frequencies of malar rash, arthritis, renal disorder, and hematologic disorder between MMF and non-MMF groups in total SLE patients. In subgroup analysis of hematologic abnormalities in total patients, frequency of leukopenia was significantly different between the two groups during follow-up (P = 0.001), but frequencies of hemolytic anemia, lymphopenia, and thrombocytopenia were not. In addition, frequencies of leukopenia in patients without lupus nephritis were significantly decreased in MMF group compared to non-MMF group (P = 0.012). This study showed that MMF might be a beneficial treatment for hematologic abnormalities, especially leukopenia, in SLE. © 2019 The Korean Academy of Medical Sciences.