Background: Acute leukemia poses a significant burden to the society and the healthcare system. Advances in chemotherapeutics and hematopoietic stem cell transplantation (HSCT) have increased survival in these patients. Protein energy malnutrition (PEM) frequently complicates the clinical picture in patients with cancer, however data on the impact of PEM in patients with acute myeloid and lymphoid leukemia is limited. Methods: We utilized the 2020 National Inpatient Sample (NIS) Database in conducting this retrospective cohort study. We identified patients with acute leukemia (myeloid and lymphoid) and PEM using appropriate ICD-10 diagnostic codes. We stratified patients with acute leukemia based on the presence or absence of PEM. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of <0.05 was considered statistically significant. The aim of this study was to investigate the impact of PEM on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charge among patients with acute leukemia. Results: We identified a total of 30995 hospitalized patients with acute leukemia, of which 13.06% (4050/30995) had comorbid PEM. The overall in-hospital mortality among patients with acute leukemia was 8.95% (2775/30995). Among those with co-morbid PEM, the mortality rate was significantly higher at 12.47% (505/4050, p<0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, PEM was found to be an independent predictor of increased in-hospital mortality (adjusted OR 1.50; 95% (confidence interval [CI], 1.18 -1.91); p=0.001), longer LOS (coefficient 10.50; CI 8.59 -12.41; p<0.001), and higher total hospitalization charge ($208,308; CI $147,516- $269,100; p<0.001). Conclusions: Our analysis demonstrated that PEM was widely prevalent in hospitalized patients with acute leukemia and significantly worsened outcomes including increased in-hospital mortality, LOS, and cost of healthcare utilization. A proactive approach for prevention and early management of cancer associated malnutrition is required. Further prospective multicentric studies are needed to better describe these associations.