College students have shown elevated mental distress during the coronavirus disease of 2019 (COVID-19). The extent and persistence of mental distress as COVID-19 restrictions have continued is unclear. This study used latent profile analysis to identify student mental health risk subgroups and to evaluate subgroups in relation with substance use. A four-profile solution was supported with a sample of 930 college students (69.6% female, 58.1% White) from 11 US-based institutions. Students were characterized by
slight
mental health symptoms,
mild
mental health symptoms,
moderate-to-severe
mental health symptoms with mild psychosis/substance use, and
severe
mental health symptoms. The severe profile comprised more ethnoracial or sexual minorities and students impacted from COVID-19. Whereas the severe profile had more alcohol-related consequences, the slight profile had fewer cannabis-related consequences. COVID-19 has exacerbated college student risks for psychiatric disorders. Students of diverse backgrounds and more impacted by COVID-19 show disproportionately more mental distress and related substance use.