Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic autoimmune condition predominantly affecting female teenagers, with high morbidity and mortality. SLE onset is uncommon before the age of 10, and even rarer before the age of 5 (EocSLE). In this paper we report 6 cases of EocSLE, including clinical and laboratory findings, treatment regimens and possible pathogenic factors. Between 2012 and 2020, 142 patients were diagnosed with cSLE and followed at our service. Six of these (4.2%; F=4, M=2) were EocSLE. Age ranged from 2.3 to 4.4 years (onset of symptoms) and from 2.8 to 4.9 years (diagnosis). All patients had arthritis at diagnosis and tested positive for homogeneous nuclear pattern ANA and anti-dsDNA, in addition to hypocomplementemia. All were treated with hydroxychloroquine and glucocorticosteroids. Three required immunosuppressants. The presence of known risk factors (mainly primary immunodeficiencies) in all patients may explain the early onset of SLE, highlighting the need for more research in this subgroup and for the development of better diagnostic tools and treatments.