Our study aimed to assess the effect of weekend versus weekday hospital admissions on all-cause mortality in patients with acute myocardial infarction (AMI) and COVID-19 during the COVID-19 pandemic. We analyzed data from the National Inpatient Sample (NIS) 2020, identifying patients with co-existing AMI and COVID-19 admitted on weekdays and weekends. Baseline demographics, comorbidities, and outcomes were assessed. A multivariable regression analysis was conducted, adjusting for confounders to determine the odds of all-cause mortality. Among 74,820 patients, 55,145 (73.7%) were admitted on weekdays, while 19,675 (26.3%) were admitted on weekends. Weekend admissions showed slightly higher proportions of men (61.3% vs. 60%) and whites (56.3% vs. 54.9%) with a median age of 73 years (range: 62-82). The overall all-cause mortality had an odds ratio (OR) of 1.00 (95% CI, 0.92–1.09; P = 0.934). After adjusting for covariates, there was no significant associations between mortality and hospital type (rural: OR = 1.04; 95% CI, 0.78–1.39; P = 0.789; urban teaching: OR = 1.04; 95% CI, 0.94–1.14; P = 0.450) or geographic region (Northeast: OR = 1.16; 95% CI, 0.96–1.39; P = 0.12; Midwest: OR = 0.99; 95% CI, 0.83–1.17; P = 0.871; South: OR = 0.97; 95% CI, 0.85–1.12; P = 0.697; West: OR = 0.94; 95% CI, 0.77–1.15; P = 0.554). There was no significant difference in the rate of all-cause mortality among patients admitted for AMI and COVID-19 between weekdays and weekends.