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Background: Acute appendicitis in the pediatric population remains a diagnostic challenge for clinicians. Despite many biochemical markers, imaging modalities and scoring systems, initial misdiagnosis and complication rates are high in children. This suggests the need for investigations directed towards new diagnostic tools to aid in the diagnosis. Recent studies have shown a correlation between serum sodium levels and complicated appendicitis. Although the exact reasons for hyponatremia in patients with complicated appendicitis are not known, there is persuasive data to support the role of pro-inflammatory cytokines such as IL-6 in the non-osmotic release of antidiuretic hormone. This meta-analysis aims to investigate all available data on hyponatremia as a diagnostic marker of complicated appendicitis in the pediatric population. Methods: The literature search was conducted by two independent investigators according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The scientific databases (PubMed, EMBASE, Web of Science, and Scopus) were systematically searched for relevant studies using the keywords (hyponatremia) AND (appendicitis) AND (children). The methodological quality was assessed using a validated scale, and RevMan 5.4 software was utilized for pooled analysis. Results: Seven studies were included in the final meta-analysis, five of which were retrospective. A total of 1615 and 2808 cases were distributed into two groups: group A with complicated appendicitis and group B with uncomplicated acute appendicitis, respectively. The studies compared serum sodium levels of patients among the groups. Pooling the data demonstrated significantly lower serum sodium levels in children with complicated appendicitis vs. the non-complicated appendicitis (WMD: −3.29, 95% CI = −4.52 to −2.07, p < 0.00001). The estimated heterogeneity among the included studies was substantial and statistically significant (I² = 98%, p < 0.00001). Conclusion: The results of the present meta-analysis indicate that hyponatremia has potential to be utilized as a biochemical marker in the diagnosis of complicated appendicitis in the pediatric population. However, well designed prospective diagnostic efficiency studies are essential to consolidate the association between hyponatremia and complicated acute appendicitis. Full article