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Background: The novel coronavirus 2019 (COVID-19) pandemic impacted everyday life for most individuals, including students. Unique COVID-19 stressors among students may include virtual learning, mental stress, and being socially distanced from classmates. Studies examining the impact of COVID-19 on stress and lifestyle changes among pharmacy students are limited. Objective: The primary purpose of this study was to compare stress and food or housing insecurity changes associated with COVID-19 in U.S. Doctor of Pharmacy (PharmD) students pre-COVID vs. during-COVID. Methods: A 23-item survey was administered via Qualtrics® to multiple PharmD programs across the U.S. in pre-COVID-19 (spring 2019) and during-COVID-19 (spring 2021). Participants were recruited via e-mail. The survey included questions related to demographics, lifestyle (sleep, exercise, work hours, extracurricular activities), and food and housing insecurities. The survey also included a validated instrument to measure stress (Cohen-Perceived Stress Scale). Results from 2021 were compared to a similar national survey serendipitously administered prior to COVID-19 in Spring 2019. Results: Pre- and COVID-19 analytical cohorts included 278 and 138 participants, respectively. While pre-COVID-19 students were slightly older (29.9 ± 4.7 vs. 27.7 ± 4.2, p ≤0.001), relative to COVID-19 students, other demographic factors were similar. No significant difference was observed in reported stress levels (PSS = 20.0 ± 6.3 vs. 19.7 ± 6.2, p = 0.610) between time periods. Significant differences in food (53.2% vs. 51.4%, p = 0.731) and housing (45.0% vs. 47.1%, p = 0.680) insecurity were also not seen. Conclusions: These findings highlight that PharmD students' perceived stress and food and housing insecurities due to COVID-19 may have been minimal. Additional studies on pharmacy students should be conducted to validate these results. These results may help inform policymakers and stakeholders during the early stages of any future pandemics.