To date, there has been relatively little published research on the mental health impacts of COVID-19 for the general public at the beginning of the U.S.' experience of the pandemic, or the factors associated with stress, anxiety, depression, and post-traumatic growth during this time. The current study provides a longitudinal examination of the predictors of self-reported stress, anxiety, depression, and post-traumatic growth for U.S. residents between April and May, 2020, including the influence of demographic, psychosocial, and behavioral factors on these outcomes. The findings indicate that, generally, the early months of the U.S. COVID-19 experience were characterized by a modest negative impact on mental health. Younger adults, people with pre-existing health conditions, and those experiencing greater perceived risk, higher levels of rumination, higher levels of co-rumination, greater social strain, or less social support reported worse mental health. Positive mental health was associated with the adoption of coping strategies, especially those that were forward-looking, and with greater adherence to national health-protection guidelines. The findings are discussed with regard to the current status of health-protective measures and mental health in the U.S., especially as these impact future management of the on-going pandemic.