Before the COVID-19 pandemic, undergraduate students experienced sleep problems and mental health issues that were negatively associated with academic achievement. Studies comparing undergraduate sleep and health pre-to mid-pandemic have yielded mixed results, necessitating additional research on other cohorts and examination of potential moderators. The present study was conducted to examine whether American undergraduate students tested mid-pandemic experienced poorer sleep, health, and academic achievement relative to students tested pre-pandemic, as well as to examine whether poor sleep during the pandemic was preferentially associated with poorer health in women. The current cross-sectional study included 217 participants tested pre-pandemic (February-December 2019) and a separate sample of 313 participants tested mid-pandemic (November-December 2020). Participants in both samples provided demographic information and completed questionnaires inquiring about participant sleep quality, insomnia, and cumulative grade point average (GPA); participants in the mid-pandemic sample also reported on measures of general, physical, and mental health. Participants tested mid-pandemic reported poorer global sleep quality, greater insomnia severity, greater stress, and higher cumulative GPAs relative to participants tested pre-pandemic. For the mid-pandemic sample only, poorer sleep quality was associated with reduced physical health; interactions indicated that women with poor sleep quality reported poorer mental health relative to both women with good sleep quality and men with poor quality sleep. Perceived stress mediated the association between sleep problems and GPA. These findings indicate that the pandemic negatively impacted the functioning of undergraduate students and highlights the need for future studies examining additional moderators of the reported effects.