The COVID-19 pandemic substantially changed daily life in ways that may impact mental health. This study compared a nationally representative online sample of 2,032 U.S. adults in late April 2020 to 19,330 U.S. adult internet users who participated in the 2018 National Health Interview Survey (NHIS) using the Kessler-6 scale of mental distress in the last 30 days. Compared to the 2018 NHIS sample, U.S. adults in April 2020 were eight times more likely to fit criteria for serious mental illness (27.7% vs. 3.4%) and three times more likely to fit criteria for moderate or serious mental illness (70.4% vs. 22.0%). Differences between the 2018 and 2020 samples appeared across all demographic groups, with larger differences among younger adults and those with children in the household. These considerable levels of mental distress may portend substantial increases in diagnosed mental disorders and in the morbidity and mortality associated with them.