This study investigates whether worsening mental health has played a significant role in the rising mortality rates experienced by some population groups in the early 21st century, a question that has gained prominence with increased attention to so-called “deaths of despair.” The main takeaway is that although declining psychological health has likely contributed to adverse mortality trends—especially among prime-age non-Hispanic Whites—its overall impact is limited and not well captured by standard definitions of “deaths of despair.” Five key findings support this conclusion. First, mental health deteriorated between 1993 and 2019 for all population groups examined. Second, these declines are associated with higher predicted death rates and help explain worsening mortality trends for prime-age non-Hispanic Whites and, to a lesser extent, non-Hispanic Blacks between 1999 and 2019. Third, while these correlations lend some support to the broader idea of “deaths of despair,” the specific causes comprising them appear to be both more expansive and different from those previously emphasized. Fourth, heterogeneity in how worsening mental distress affects mortality—rather than in mental health trends themselves—is more important in explaining Black-White disparities in its overall impact. Finally, in the primary specifications, deteriorating mental health accounts for an estimated 9 % to 29 % of the rise in mortality rates among prime-age Whites in recent years.