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<b>Background</b>: Acute appendicitis, a frequent pediatric surgical emergency, requires distinguishing simple from complicated cases for treatment decisions. Current tools, such as clinical scores and ultrasound, are sometimes ineffective. This study evaluates the biomarkers: neutrophils to lymphocytes ratio (NLR), monocytes to lymphocytes ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophils to monocytes ratio (NMR), neutrophils to platelet ratio (NPR), pan-immune-inflammation value (PIV) ratio, and C-Reactive Protein (CRP) to lymphocytes ratio (CLR) for differentiation between simple and complicated appendicitis. <b>Methods</b>: A retrospective study of 878 pediatric patients (<18 years) who underwent appendectomy (2018-2024) at a tertiary medical center, with appendicitis classified as simple (SA, <i>n</i> = 696) or complicated (CA, <i>n</i> = 182) using intraoperative findings. Biomarkers were calculated from preoperative blood counts and CRP. Diagnostic accuracy was assessed using Mann-Whitney U tests, ROC curves, and logarithmic regression. <b>Results</b>: Patients with CA had higher neutrophils counts (13.61 ± 4.92 vs. 11.39 ± 4.29 K/μL), monocytes counts (1.23 ± 1.41 vs. 0.95 ± 0.48 K/μL), platelet counts (294.31 ± 72.73 vs. 270.15 ± 72.08 K/μL), CRP levels (88.55 ± 97.75 vs. 27.15 ± 44.74 mg/L), and elevated biomarker ratios as compared to those with SA: NLR (≥10.15, OR = 2.45), MLR (≥0.645, OR = 2.78), PLR (≥224.38, OR = 2.502), NMR (≥6.38, OR = 2.34), NPR (≥0.0405, OR = 1.876), PIV (≥2433.85, OR = 3.348), and CLR (≥11.77, OR = 5.935), all at <i>p</i> < 0.01. CLR demonstrated the highest accuracy (AUC = 0.772, sensitivity 78%, specificity 62.6%), outperforming established biomarkers, followed by PIV (AUC = 0.679). NPR was the least effective marker (AUC = 0.569). <b>Conclusions</b>: CLR, a promising biomarker, can aid in distinguishing complicated from simple appendicitis in children, and may offer accessible tools for resource-limited settings.