Past studies have found that university students' well-being is relatively low, and that first-year students are specifically vulnerable. This issue has drawn particular attention during the COVID-19 pandemic. This study examines the effect of COVID-19 on the well-being, academic confidence, feeling of informedness, and self-efficacy of first-year university students. Both cross-sectional and longitudinal data were used. Survey data were collected from two cohorts of first-year students at a Belgian university (N = 997): a pre-covid cohort (N = 493) and a covid-affected cohort (N = 504). Data were gathered at two measurement moments for the pre-covid cohort and at four measurement moments for the covid-affected cohort. First, between-subject analyses (ANCOVA) revealed no significant effect of COVID-19 on students' well-being (p > 0.100), academic confidence (p > 0.100), and feeling of informedness (p > 0.100), on arrival at university. Three weeks later, however, the covid-affected cohort reported (marginally) lower well-being than the pre-covid cohort (p = 0.057, n[superscript 2] = 0.01). Second, longitudinal analyses (repeated measures ANCOVA) on the COVID-affected cohort revealed changes throughout the academic year in well-being (p < 0.001, n[subscript p] [superscript 2] = 0.39) and self-efficacy (p < 0.001, n[subscript p] [superscript 2] = 0.04). Well-being and self-efficacy decreased during the first semester (p < 0.001), and slightly recovered at the start of the second semester (p < 0.001). Educational implications on how to support students during their transition to higher education are discussed.