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Introduction: Sepsis, a syndrome of organ dysfunction caused by an unregulated host response to infection. This study aimed to develop a novel sepsis diagnostic model of hematological parameters and evaluate its effectiveness in the early identification and prognosis of sepsis in emergency departments. Methods: A retrospective study was conducted in Emergency Department. Cell population data parameters related to monocytes and neutrophils were obtained using the Mindary BC‐6800 plus hematology analyzer. Receiver operating characteristic (ROC) curve analysis, logistic regression analysis was performed to assess the performance of the parameters and establish a diagnostic and prognostic model of sepsis, which was then verified with a validation cohort. Results: Mon_XW exhibited the best diagnostic performance (area under the ROC curve [AUC] = 0.848, 95% confidence interval [CI]: 0.810–0.885, p < 0.001), followed by Neu_Y and Neu_YW (AUC = 0.777 95% CI: 0.730–0.824, p < 0.001). Logistic regression analysis identified Mon_XW and Neu_Y as independent predictors, which were used to establish a diagnostic model named hematological parameter for sepsis (HPS). HPS demonstrated the best diagnostic performance with an AUC of 0.862 (95% CI: 0.826–0.898, p < 0.001), sensitivity of 70.0%, and specificity of 87.1%, compared to C‐reactive protein (CRP) and procalcitonin (PCT). The validation cohort also found that the positive predictive value of HPS was 70.4% and the negative predictive value was 92.2%. Conclusion: The developed HPS model showed promising diagnostic efficacy for sepsis in the emergency department, which outperformed CRP and PCT in terms of sensitivity and specificity. By enabling early identification and prognosis of sepsis, that contributes to reducing sepsis‐related mortality. [ABSTRACT FROM AUTHOR]