Background: Tumor lysis syndrome (TLS) is a well-known complication of hematological malignancies including leukemia and lymphoma which can occur after chemotherapy or spontaneously, early recognition of TLS can be challenging sometimes. We attempted to evaluate the Weekend effect on TLS outcomes. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) was queried to identify TLS admissions between 2016-2018 in patients with diagnosis of acute leukemia and lymphoma. We studied socio-demographic differences, all-cause mortality, acute renal failure and dialysis. Secondary outcomes included mean length of stay (LOS), mean total hospital charges (THC). Statistics were performed using the t-test, univariate and multinomial logistic regression. Results: A total 1595 TLS admissions were identified (51% in lymphoma and 49% in acute leukemia), weekend admissions were 14.4% of total admissions. There was no significant difference in the baseline characteristics between the 2 groups including mean age, sex, race, median household income national quartile for patient zip code, insurance, region of hospital and location/teaching status of the hospital. Total 195 (12%) patients died in the total study group; Mortality rate among patients with lymphoma was 16% while those with leukemia was 9%. Overall mortality rate among the Weekend group compared to weekday group was insignificantly higher (20% vs 11% with P = 0.11, aOR 1.4 CI 0.56-3.46 p = 0.53). Mortality in the Weekend group was significantly higher in patients with lymphoma (30% vs 13% P = 0.04) while in leukemia patients there was no significant weekend effect (8% vs 9% P = 0.83). Total 1170 patients developed acute renal failure (aOR 1.56 Cl 0.64-3.9 p 0.32) of which 30 required dialysis, none of them was admitted in the weekend group. Mean LOS for the whole cohort was 6.47 days and mean THC was $94,954 with no significant difference between the 2 groups. Conclusions: All-cause mortality was significantly higher in patients with TLS and lymphoma admitted on the weekend (p = 0.04) compared to weekday while no weekend effect was found in TLS admissions in leukemia. Further studies are needed to clarify if this higher mortality may be associated with delay in TLS diagnosis over weekend admissions in lymphoma patients.