The objective of the study was to develop and validate a prediction model that identifies COVID-19 patients at risk of requiring oxygen support based on five parameters: C-reactive protein (CRP), hypertension, age, and neutrophil and lymphocyte counts (CHANeL). This retrospective cohort study included 221 consecutive COVID-19 patients and the patients were randomly assigned randomly to a training set and a test set in a ratio of 1:1. Logistic regression, logistic LASSO regression, Random Forest, Support Vector Machine, and XGBoost analyses were performed based on age, hypertension status, serial CRP, and neutrophil and lymphocyte counts during the first 3 days of hospitalization. The ability of the model to predict oxygen requirement during hospitalization was tested. During hospitalization, 45 (41.8%) patients in the training set (n = 110) and 41 (36.9%) in the test set (n = 111) required supplementary oxygen support. The logistic LASSO regression model exhibited the highest AUC for the test set, with a sensitivity of 0.927 and a specificity of 0.814. An online risk calculator for oxygen requirement using CHANeL predictors was developed. “CHANeL” prediction models based on serial CRP, neutrophil, and lymphocyte counts during the first 3 days of hospitalization, along with age and hypertension status, provide a reliable estimate of the risk of supplement oxygen requirement among patients hospitalized with COVID-19.