Background: To investigate the relationship between lactate dehydrogenase and apolipoprotein A1 levels and the condition and prognosis of patients with severe pneumonia. Methods: Data was collected from 204 patients with severe pneumonia who were hospitalized from January 1, 2019 to December 1, 2021 in Zhaotong First People's Hospital (respiratory intensive care unit (RICU)), and divided into survival group (160 patients) and death group (44 patients) according to their hospitalization outcome. The relationship between lactate dehydrogenase and apolipoprotein A1 levels and general information, disease, and treatment needs of patients with severe pneumonia was analyzed, and lactate dehydrogenase, apolipoprotein A1, neutrophil-to-lymphocyte ratio, hematocrit, C -reactive protein, calcitoninogen, D-dimer, Acute Physiology and Chronic Health Status Rating System II, and Pneumonia Severity Index scores were compared between the survival and death groups. The value of these indicators in determining the prognosis of patients was analyzed using subject operating characteristic (ROC) curves. Logistic regression was used to analyze the risk factors for death from severe pneumonia. Results: The age and pneumonia type differed significantly between the two groups (P<0.05). There were no significant differences in gender and total hospitalization days (P>0.05). LDH (Lactate Dehydrogenase) and ApoA1 (Apolipoprotein A1) levels showed significant differences among different age groups with severe pneumonia (P<0.05). LDH and ApoA1 levels did not differ signifi cantly between SCAP (Severe Community -Acquired Pneumonia) and SHAP (hospital -acquired pneumonia) patients (P>0.05). LDH and ApoA1 levels were higher in severe pneumonia patients with acute exacerbation or MODS (multiple organ dysfunction syndrome), compared to those without (P<0.05). LDH and ApoA1 levels varied significantly with PSI (Pneumonia Severity Index) grades or APACHE II (Acute Physiology and Chronic Health Evaluation II) scores, ICU stay duration, and mechanical ventilation duration in severe pneumonia patients (P<0.05). The LDH and ApoA1 levels were significantly higher in the deceased group compared to the survival group (P<0.05). neutrophil-to-lymphocyte ratio (NLR), hematocrit (HCT), C -reactive protein (CRP), calcitoninogen (PCT), D-dimer (DD), PSI scores, and APACHE II scores did not show significant differences between the two groups (P>0.05). LDH and ApoA1, when combined, had a higher predictive value for severe pneumonia mortality (Area Under the Curve, AUC=0.873, P<0.05). Multivariate logistic regression analysis confirmed that LDH>289 U/mL and ApoA1<0.92 mg/mL increased the risk of severe pneumonia mortality (OR=4.275, 0.548, P<0.05). Conclusion: Elevated LDH levels and reduced ApoA1 levels in patients with severe pneumonia are valuable in assessing patients' conditions and prognosis, and can provide assistance in the early assessment of patients' conditions and diagnosis and treatment.