Many studies have shown that patients admitted to the hospital on the weekend experience more preventable complications and are at increased risk for mortality. The mechanism for this finding is unknown and could be due to health care system factors (i.e., lower weekend staffing and availability of clinical services) or patient factors (i.e., those admitted on weekends could be more complex and at higher risk of death than weekday admissions). This population-based analysis from New South Wales, Australia sought to determine the contribution of health care system and patient factors to elevated weekend mortality by analyzing daily mortality rates for the 7-day period following weekend admission. For certain diagnoses, such as pulmonary embolism, the risk of death was elevated during the first 48 hours after weekend admission but declined thereafter, implying that health care system factors are the primary driver of the weekend effect. However, patients with cancer-related diagnoses continued to have elevated mortality risk for the full 7 days after weekend admission, implying that patient factors such as illness severity are the major contributor to excess mortality. Other diagnoses, such as stroke, showed a mixed pattern of system and patient factors. By providing a nuanced view of the types of diagnoses and factors associated with the weekend effect, this study demonstrates the need for tailored solutions for this well-documented problem.