BackgroundAt the time of this study, Massachusetts had recorded a total of 352,558 COVID-19 cases and 12,076 deaths. Few qualitative studies have been conducted that investigate the experiences of university students and employees during the COVID-19 pandemic. The objective of this study was to explore the knowledge, attitudes, and practices regarding COVID-19 in university affiliates to inform future COVID-19 policies.MethodsSemi-structured focus groups and interviews were conducted via Zoom between December 14, 2020 and January 15, 2021. Twenty-two focus group participants included undergraduate students, graduate students and university employees who had not experienced isolation or quarantine during the Fall 2020 semester. Fourteen participants who had experienced quarantine or isolation were interviewed individually to protect confidentiality. Data were analyzed using Dedoose software via inductive thematic analysis, with reporting as per Consolidated Criteria for Reporting Qualitative Studies (COREQ) guidelines.ResultsFive major themes emerged from these data: COVID-19 knowledge, stress and coping, trust, decision-making, and institutional feedback. Misinformation regarding COVID-19 was common, compounding high levels of stress reported by many participants. Reported direct sources of stress included physical illness, fear of infection, and lack of access to resources while in quarantine or isolation settings. Reported indirect sources of stress included social isolation and financial constraints. Levels of trust were generally high regarding mainstream news media, scientific journals, and university-related information sources. For decision-making processes, participants described altered behaviors to socialize safely during the pandemic, which included increased testing, gathering outdoors, and limiting group sizes. Conversely, some undergraduate students reported increases in socialization behaviors after testing negative for COVID-19, while most university employees did not report altered behaviors after negative test results. While some participants described negative feedback regarding university decisions, most feedback for the institution was positive, with participants reporting appreciation for the university’s asymptomatic testing program and other on-campus health response activities.ConclusionThe university’s investment in COVID-related resources, including the asymptomatic testing program and the on-campus quarantine and isolation spaces, were reported to greatly reduce stress and increase perceived safety. Key findings from this research could guide institutional communication, public health protocols, and support for university community members.