Background <p>Childhood-onset systemic lupus erythematosus (cSLE) is a rare and severe autoimmune disorder with impactful physical and psychological impacts. While depression and anxiety are well-recognized in adult SLE, their incidence and determinants in cSLE remain less clear.</p> Methods <p>We performed a systematic review and meta-analysis following PRISMA guidelines. We searched five databases from inception to January 2025. Our inclusion criteria were studies of pediatric patients (≤18 years) meeting 1997 ACR, and 2021 SLICC diagnostic criteria for SLE and reporting anxiety or depression rates. Data of the demographics, disease characteristics, and medications were extracted, and meta-regression explored potential determinants.</p> Results <p>36 studies fulfilled inclusion criteria. Pooled analyses revealed a 14% prevalence of anxiety and 19% prevalence of depression. Exploratory meta-regression indicated that immunosuppressive therapies were associated with modest but statistically significant reductions in both depression and anxiety. By contrast, hematologic complications showed a positive association with risk of mood disorders. Oral steroids showed inconsistent relationships with psychological outcomes.</p> Conclusions <p>Anxiety and depression are common in cSLE, we need to integrate screening for them in rheumatologic and mental health care. Close monitoring, early screening, and targeted interventions can help detect the psychological burden and potentially improve adherence to therapy and long-term outcomes.</p> Trial registration number <p>Not applicable.</p>