OBJECTIVE Macrophage activation syndrome (MAS) is a severe complication of juvenile systemic lupus erythematosus (jSLE). However, little is known about the association between these conditions, especially in terms of MAS as the initial manifestation of jSLE. The aim of this study was to determine the clinical features of MAS as the initial manifestation of jSLE. METHODS We carried out a retrospective review of the clinical features of MAS cases diagnosed concomitantly with jSLE from 2004 to 2016. Data from these patients were compared with those from a control group consisting of jSLE patients without MAS. RESULTS Eleven (23.9%) of the 46 patients recruited for this study were diagnosed with MAS during the initial stage of jSLE. The between-group comparisons demonstrated that fever, leucopenia, hyperferritinaemia and increased aspartate aminotransferase were more frequently observed in jSLE patients with MAS than in controls (P<0.01). Importantly, neurological symptoms were significantly more common in patients with MAS than in controls (P<0.01), with 6 (54.6%) of the 11 MAS patients affected. For treatment, all 11 patients with both jSLE and MAS were administered CSs upon diagnosis, and 7 received immunosuppressants. No patient involved in this study died. CONCLUSIONS MAS can develop as the initial manifestation of jSLE. MAS with jSLE should be suspected in patients with fever, hyperferritinaemia, cytopenia and liver disorder. In addition, we found that jSLE patients with MAS had more neurological symptoms than those without. All patients with MAS were successfully treated with CSs. Early diagnosis and intensive therapy are essential in improving clinical outcomes.