Social isolation and loneliness are prevalent in the U.S., and they have harmful effects on heart and brain health. Older adults and people in socially vulnerable groups, such as individuals from disenfranchised racial or ethnic groups, people with disabilities, or those who are members of gender or sexual minority groups, may be at increased risk for social isolation and loneliness. Data also suggests that social isolation and loneliness may have increased among many groups during the COVID-19 pandemic. More research is needed to develop and implement public health interventions to reduce the adverse effects of social isolation and loneliness on cardiovascular health.