This paper examines the relationship between extreme socioeconomic disadvantage and poor health by providing the first detailed and accurate picture of mortality patterns among people experiencing homelessness in the U.S. Our analyses center on 140,000 people who were sheltered or unsheltered homeless during the 2010 Census, by far the largest sample ever used to study this population and the only sample designed to be nationally representative. These individuals, along with housed comparison groups, are linked to Social Security Administration data on all-cause mortality from 2010-2022 to estimate the magnitude of health disparities associated with homelessness. We find that non-elderly people experiencing homelessness have 3.5 times the mortality risk of those who are housed, accounting for differences in demographic characteristics and geography, and that a 40-year-old homeless person faces a similar mortality risk to a housed person nearly twenty years older. Our results reveal notable patterns in relative mortality risk by age, race, gender, and Hispanic ethnicity and suggest that within the homeless population, employment, higher incomes, and more extensive observed family connections are associated with lower mortality. The mortality hazard of homeless individuals rose by 33 percent during the COVID-19 pandemic, an increase that, while similar in proportional terms to the increase for the housed population, affected a much larger share of the homeless population due to their substantially elevated baseline mortality rate. These findings elucidate the persistent hardships associated with homelessness and show that the well-documented gradient between health and poverty persists into the extreme lower tail of socioeconomic disadvantage.