Objective: It is known that age at disease onset has an impact on the clinical course andoutcome of systemic lupus erythematosus (SLE); however, the precise differences in theprevalence of SLE manifestations are debated. Our objective was to conduct a systematicliterature review and meta-analysis of all studies that directly compare childhood-onset lupus with adult-onsetlupus to determine which clinical manifestations vary with age at disease onset. Methods: A comprehensive literature search of the MEDLINE/PubMed,EMBASE, CINAHL, and SCOPUS databases was conducted to identify relevant articles. Study quality was assessed using the STROBE checklist. Study sample characteristics and clinical manifestation event rates were extracted from each study. Pooled odds ratios (ORs) were calculated using the random effects method, and between-study heterogeneity was quantified using the I 2 statistic. Results: Of the 484studies identified by the search strategy, 16 were included in this review. The total number of patients was 5993 adults and 905 children with SLE. Study quality was on average 16/32, ranging from 8 to 29. Several statistically significant differences were found: malar rash, ulcers/mucocutaneous involvement, renal involvement, proteinuria, urinary cellular casts, seizures, thrombocytopenia, hemolytic anemia, fever, and lymphadenopathy were more common in childhood-onset SLE with ORs ranging from 1.3 to 3.7; however, Raynaud’s, pleuritis, and sicca were more common in adult-onset SLE (twice as common). Conclusions: The results of this meta-analysis suggest that some clinical manifestations of lupus are different in childhood-onset SLE and adult-onset SLE.