Objective: To examine the relationship between college student anxiety, optimism, gratitude, and perception of the Physical Activity and Lifestyle program (PAL) instructional response/effectiveness following COVID-19. Participants: Data were collected from a southeastern, midsize university (n = 1640) during April 2020. Methods: Participants responded to a Web-based survey that included mental health factors (optimism, gratitude, anxiety) and perceptions of COVID-19 academic response. Results: The results of this study revealed a significant, negative relationship between anxiety and optimism (r = 0.36), gratitude (r = -0.12), and perceived instruction following COVID-19 (r = -0.11). There were statistically significant differences in perceived PAL instructional response/effectiveness following COVID-19 between anxiety classification, with severely anxious students expressing lower instructional response to COVID-19 when compared to moderately or mildly anxious students, [F(2,1516) = 10.60, p < 0.001]. Conclusions: The results inform educators on the importance of effective education and coping strategies following online transition during a pandemic.