On March 11, 2020 the World Health Organization declared COVID-19 infection a global pandemic, prompting closures and other restrictions across the world. A substantial proportion of the world population was suddenly homebound, giving us all a small glimpse into the experiences of the approximately 6% of US older adults who were already homebound. Further closures and restrictions have been implemented worldwide in relation to the second wave of the infection. This raises questions about the effects that social isolation may have on our mental and physical well-being. Public health concerns about social isolation and loneliness were growing internationally even prior to the pandemic. In 2018, the UK appointed a Loneliness Minister and published a national strategy for tackling loneliness. In the US, the National Academies of Sciences, Engineering, and Medicine released, just two weeks prior to the declaration of the pandemic, an expert consensus report on the relevance of social isolation and loneliness in older adults for the health care system1. Nonetheless, social isolation and loneliness have generally been underrecognized and underappreciated relative to the evidence supporting their public health importance2. Evidence suggests that a significant portion of the population was already socially isolated, lonely, or both, prior to the pandemic2. Social isolation refers to objectively being alone, having few relationships or infrequent social contacts; whereas loneliness refers to subjectively feeling alone, or the discrepancy between one’s desired level of connection and one’s actual level. While international standardization of measurement and classification is needed to provide more precise estimates of prevalence and changes over time, substantial evidence from both national and international surveys raise concern. Several surveys suggest that loneliness has increased by 20-30% during the pandemic. Loneliness can occur across age, income levels, living situations and gender; however, rates are highest among those at younger ages, with lower incomes, and with chronic health conditions1, 3. These risk factors are similar to those identified pre-COVID3. In the midst of a global pandemic, the immediate dangers of a deadly novel virus are understandably being prioritized. However, social isolation and loneliness can result in both short- and long-term health effects that cannot be ignored. The lethal effects of social isolation and loneliness may be more immediate, in the case of suicide or domestic violence, or more long-term, in the case of disease-related deaths. International data from over 3.4 million people demonstrate the association of social isolation and loneliness with a significantly increased risk of death from all causes4. Conversely, being socially connected is protective and increases odds of survival by 50%5. Cumulative evidence over decades of research demonstrates that the magnitude of mortality risk related to social isolation and loneliness is comparable with or exceeds the risk associated with other known public health problems (e.g., obesity, air pollution)2. Further, there is compelling evidence that social isolation and loneliness significantly contribute to morbidity, particularly cardiovascular disease and stroke1. Furthermore, social isolation and loneliness influence problematic health behaviors, including substance use, poorer sleep and poorer eating habits. Lacking proximity to others, particularly trusted others, may result in a state of alertness both centrally and peripherally. Problematic behaviors and physiological changes may potentially exacerbate or precipitate the onset of acute events among those with pre-existing diseases6. Social isolation and loneliness may even influence susceptibility to the COVID-19 infection. They predict worse mental health, and individuals with mental health conditions are more likely to be socially isolated and lonely1. This bidirectional association is noteworthy, since an analysis of population-wide electronic health records has found that people with a mental health diagnosis are more likely to be infected and hospitalized and to die from COVID-197. Furthermore, a recent paper summarizing evidence from a 35-year research program found that people experiencing interpersonal stressors such as loneliness had a greater chance of developing an upper respiratory illness when exposed to cold viruses8. Steps to limited social contact associated with the global pandemic are becoming more persistent in nature, and both short-term and longer-term public health concerns will emerge if the effects of social isolation and loneliness are not mitigated. We cannot take an either-or position, pitting the dangers of COVID-19 against the dangers of social isolation and loneliness. We must find a way to address both risks to promote public health. What are actionable steps that can prevent or reduce COVID-19-related isolation and loneliness? A systems approach recognizes that individual, community and societal factors are interdependent and may all contribute to social isolation and loneliness9, and thus each of these levels need to be considered and targeted. At the individual level, research has shown that high-quality interactions among household members, interacting with neighbors, providing support to others, and expressions of gratitude, all promote social bonds and are negatively correlated with loneliness. At the community and societal level, we have already seen changes in social norms and physical spaces, all aimed at reducing social contact, that may have longer-term public health implications if not mitigated. Community and national leaders should foster norms of support, inclusion and trust, leading to a greater sense of security, an essential component of feeling socially connected to a group. The relevance of every sector of society not only for COVID-19-related but also for isolation-related public health risks is readily apparent. Thus, we should begin to evaluate existing local and national policies across sectors (health care, transportation, education, housing, employment, nutrition, and environment) aiming to preserve and promote the quality of social contacts. The social needs of the population need to be at the forefront of every pandemic and recovery plan. It is not clear how long the social and health ramifications of the COVID-19 restrictions will persist. As we create our “new normal” adaptations to the pandemic, they may become more permanent. For example, remote working is becoming the norm and digital tools are increasingly being adopted or required; however, little is known about their equivalence to in-person contact and their influence on social and health outcomes. There is an urgent need for rigorous scientific evaluation of these practices and policies.