This study aimed to assess the potential of thrombospondin 1 (TBS-1) as a biomarker for pediatric-onset systemic lupus erythematosus (pSLE) and investigated its association with clinical characteristics and other laboratory tests in pSLE. A total of 112 pSLE and 50 age-matched and gender-matched healthy controls (HCs) were recruited in this study from January 2022 to June 2023 at West China Second University Hospital, Sichuan university. Plasma TBS-1 levels were measured, and clinical and laboratory findings were collected from the medical database. The plasma TBS-1 level was significantly lower in pSLE patients (26778 ng/mL, IQR: 9875–59011) compared to HCs (100583 ng/mL, IQR: 58327–189547) (P < 0.0001). ROC analysis demonstrated that TBS-1 could effectively differentiate pSLE patients and HCs (AUC: 0.845, 95%CI: 0.785–0.905, P < 0.0001) with an optimal cut-off was 49,937 ng/mL, yielding a sensitivity of 84% and specificity of 70.5% based on the Youden index. Compared to TBS-1 positive patients, TBS-1 negative patients exhibited significant reductions in hemoglobin, IgM, and fibrinogen levels. In light of the current data, the efficacy of TBS-1 as a biomarker in pSLE diverged from its performance in adult SLE. In summary, TBS-1 shows potential as a biomarker for pSLE, particularly in hematological manifestations. Further investigations are essential to delve into the immunomodulatory roles of TBS-1 in the autoimmune pathways of pSLE.