To understand the role and future implications of social distancing on mental health and substance use in young adults between the ages of 18 and 35 living in high-disease-prevalent areas of New York. Participants completed a self-administered online survey through Qualtrics. 43.9% of the sample met criteria for moderate or severe anxiety, and 53.1% of the sample met criteria for moderate to severe depression. 76.1% of the sample experienced both anxiety and depressive symptoms. Despite this, the rates of lifetime mental health diagnoses, treatment, and access to mental health services were low. Rates of depression and anxiety differed across socio-demographic variables (gender, income, sexuality, education, and insurance status). Experiencing severe symptoms of the COVID-19 virus, poor coping skills, loneliness, increased alcohol use, and sleep disturbances were linked to higher rates of depression, anxiety, or both. As the first epicenter of COVID-19 in the United States, New York represents an important location for prevention researchers to learn about how COVID-19 affected a diverse population of young adults. It is essential that researchers and practitioners proactively develop early and appropriate interventions to address the ongoing mental health crisis and also plan for future crises.