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Background: The aim was to explore the value of combined detection of PCT, CRP, and FIB in differentiating severe pneumonia from viral infection and bacterial infection. Methods: A total of 100 patients with severe pneumonia admitted to Hebei General Hospital from August 2020 to November 2021 were selected as the research objects, including 50 patients with viral pneumonia (as the viral group, n = 50) and 50 patients with bacterial pneumonia (as the bacterial group, n = 50). At the same time, the clinical data of 50 healthy people in the hospital were selected as the healthy group (n = 50). All the subjects in the three groups were tested for PCT, CRP, and FIB. The difference of each index level among the three groups was compared. The diagnostic efficacy of each index for pneumonia was analyzed by drawing receiver operating characteristic curves, and the independent predictors of pneumonia were determined by logistic regression model. Results: There were no statistically significant differences in gender, age, course of disease, body mass index (BMI), and other general data among the three groups (p > 0.05). Compared with the healthy group, the levels of serum PCT, CRP, and FIB in the viral group and the bacterial group were significantly increased, and the levels of serum PCT, CRP, and FIB in the bacterial group were significantly higher than those in the viral group, and the differences were statistically significant (p < 0.05). The positive rates of FIB, CRP, and PCT in bacterial group and viral group were increased in turn, and the differences were statistically significant (p < 0.05), and the positive rates of combined detection in the two groups were significantly higher than the positive rates of single index detection (p < 0.05). Taking etiological examination as the gold standard, the sensitivity (92.59%) and specificity (90.17%) of the three combined detection methods were significantly higher than those of PCT, CRP, and FIB alone. Kappa test showed that the results of the combined detection and etiological examination were in good agreement (Kappa value = 0.847, p < 0.05). ROC curve analysis showed that the AUC of combined prediction of the three was 0.964, which was higher than that of single detection of 0.859, 0.832, and 0.871. Logistic regression analysis showed that serum PCT, CRP, and FIB were independent predictors of bacterial pneumonia, and the differences were statistically significant (p < 0.05). Pearson's correlation analysis showed that FIB level in the bacterial group was positively correlated with PCT and CRP. PCT was positively correlated with CRP. Conclusions: Compared with viral pneumonia, the levels of serum PCT, CRP, and FIB in patients with bacterial pneumonia are higher. Biochemical indexes can be used as independent predictors for the diagnosis of bacterial pneumonia, and have high diagnostic value. The combined detection of the three has the highest diagnostic efficiency, which is conducive to the clinical differential diagnosis of the early types of pneumonia infection. [ABSTRACT FROM AUTHOR]