It is important to identify the patients with high-risk progression to develop severe acute pancreatitis (SAP). The study was to assess whether neutrophil to lymphocyte ratio (NLR) and fluid sequestration (FS) could represent useful markers for predicting the severity. A total of 1639 patients who underwent clinical diagnosis of AP was performed. Various serologic and clinical parameters on admission were investigated. Chronologic change in NLR and FS were analyzed, and theirs utility for predicting severity of AP was evaluated by receiver operator characteristic (ROC) curve analysis. Correlation analysis was assessed by Spearman’s rank test. NLR and FS levels were both increased significantly in SAP and positively correlated with Ranson score and hospital stays. The ROC curve analyses showed the optimal cut-off values of NLR for admission with day0, day1, day2 were 9.64, 6.66 and 6.50, giving sensitivity of 77–82%. The optimal cut-off values of FS for admission with day1, day2, day3 were 1375 ml, 2345 ml and 3424 ml, giving sensitivity of 62–75%. Moreover, measurement of NLR and FS together exhibited a similar area under curve (AUC) and sensitivity for SAP prediction compared with the those of Ranson score. Increase of NLR and FS are correlated with severity and can be suggested as a predictive factor in an early stage of AP.