BackgroundHigh altitude pulmonary edema (HAPE) is a serious condition characterized by pulmonary edema occurring at high altitudes, posing a medical emergency. Biomarkers predicting HAPE severity remain elusive, prompting the exploration of accessible indicators such as Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-toLymphocyte Ratio (PLR). This study aimed to assess the predictive role of NLR and PLR in HAPE severity, alongside analyzing its clinical profile and outcomes. MethodsA single-center cross-sectional comparative study was conducted in a high-altitude hospital in North Sikkim. Participants underwent acclimatization at varying altitudes, with medical history and examinations recorded. HAPE severity was categorized based on symptoms, pulse, respiratory rate, and chest radiograph findings. NLR and PLR were calculated, and their association with severity, hospitalization duration, and oxygen support days were analyzed. Statistical methods included logistic regression, Receiver Operating Characteristic (ROC) curve analysis, and cutoff determination. ResultsDyspnea and cough showed significant correlation with HAPE severity. Tachycardia, tachypnea, and adventitious sounds during auscultation were significantly associated with severity. Hematological parameters revealed higher NLR and PLR in severe cases, with NLR demonstrating sensitivity and specificity in distinguishing severe from non-severe cases. ConclusionA comprehensive assessment involving clinical symptoms and hematological parameters aids in determining HAPE severity. NLR emerges as a promising, costeffective marker for severity prediction. Further research with larger cohorts and multicenter studies is needed to validate these findings and establish optimal cutoff values. Nevertheless, this study underscores the importance of accessible biomarkers in HAPE, particularly in resource-limited settings, offering valuable insights into disease severity assessment and prognosis.