Background <p>Apelin is an endogenous ligand of the apelin receptor (APJ), expressed in multiple tissues, including the brain and heart. Isoforms such as apelin-13 and apelin-36 play protective roles in pathological processes, including oxidative stress, inflammation, apoptosis, and autophagy. This study aimed to examine the relationship between apelin and oxidative stress in pediatric pseudotumor cerebri syndrome (PTCS).</p> Methods <p>In this cross-sectional, case-control study, serum samples were obtained from 33 children with PTCS and 44 age- and sex-matched healthy controls between September 2023 and August 2024. Demographic and clinical data, including age, sex, MRI findings, papilledema grade, and treatment history, were recorded. Serum apelin-13, apelin-36, total oxidant status (TOS), and total antioxidant status (TAS) were measured using ELISA.</p> Results <p>Children with PTCS demonstrated higher papilledema grades and more frequent MRI abnormalities compared with controls. Elevated apelin-13 levels were significantly associated with abnormal MRI findings (<i>p</i> = 0.022). TOS levels were lower in patients with grade 3 papilledema (<i>p</i> = 0.006). Apelin-36 levels were higher in PTCS cases and were significantly associated with treatment status (<i>p</i> = 0.022). A positive correlation was observed between apelin-13 and apelin-36 (<i>r</i> = 0.340). Regression analysis indicated that a 1-standard-deviation increase in apelin-36 was associated with a 1.035-fold increase in the risk of PTCS (<i>p</i> = 0.012).</p> Conclusion <p>Apelin-36 appears to be a promising biomarker for PTCS, reflecting both the presence and severity of the disease. Apelin-13 was associated with radiological findings of idiopathic intracranial hypertension. Further studies are warranted to clarify the role of apelin isoforms and oxidative stress markers in PTCS pathophysiology.</p>