Background: Childhood-onset systemic lupus erythematosus (cSLE) is a complex multisystem autoimmune disease often associated with pain, fatigue, and mood-related disturbances. cSLE is associated with increased disease severity and higher rates of mortality as compared to adult onset SLE. Therefore, a multi-faceted approach to care, including the use of non-pharmacologic therapies, is essential to ensure optimal patient outcomes. The use of non-pharmacologic therapies as adjunctive treatments has been shown to be beneficial in adults with SLE, yet, their use and effect is less well understood in cSLE. This is the first systematic review to explore the use and quality of evidence of non-pharmacologic approaches to treat cSLE. Methods: A literature review was performed using PRISMA guidelines. Studies until March 2021 with participants diagnosed with cSLE were included. The quality of the evidence was graded via OCEBM levels of evidence guidelines and bias assessed using Cochrane guidelines. Completed clinical trials (via clinicaltrials.gov) were also searched to identify unpublished results. Results: Eleven published studies consisting of 1,152 patients met inclusion criteria for this review, as well as 3 additional studies with unpublished data on clinicaltrial.gov. Of the published trials, four studies used patient education/support, 3 studies used dietary supplementation, 3 used forms of psychotherapy (e.g., CBT), and 1 used aerobic exercise to target the following issues: treatment adherence (n=3), quality of life (n=3), fatigue (n=2), pain (n=2), depressive symptoms (n=1), anxiety (n=1), and health-related outcomes including disease severity (n=3), cardiovascular disease risk (CVD; n=3), and muscle function (n=1). Across investigations, the quality of the evidence based on study design was moderate/low. In terms of potential outcomes, dietary supplementation methods were successful in 2 of 3 studies and were associated with improvements in disease activity and fatigue. Aerobic exercise was effective in decreasing resting heart rate and increasing cardiorespiratory capacity. Patient education/support was related to significantly increased treatment adherence and decreased cardiovascular risk markers. Two of the three studies examining the impact of psychotherapy showed improvements (e.g., in treatment adherence, depression and fatigue).