In the Fall 2020 semester, faculty at colleges and universities across the United States changed course structures in many ways to adapt to the COVID‐19 pandemic. At our institution, a regional comprehensive open‐access university in the Midwest, campus was open for in‐person courses with specific COVID precautions in place. Faculty were given substantial flexibility in how they restructured their courses, within constraints of socially distanced classrooms and accessibility for students. In prior semesters, our upper‐division undergraduate animal physiology course met fully in‐person for three 50‐minute lecture periods and one 3‐hour lab period per week. In fall 2020, a previously planned shift to a 4‐day class week had led to a change to two 80‐minute lecture periods and one 3‐hour lab period per week. To align with COVID mitigation policies, the class was further restructured to a hybrid format as follows: For lecture, half of the students attended the first in‐person class meeting of the week, and the other half attended the second in‐person class meeting of the week. The same topics were covered in both in‐person sessions in a given week and all in‐person classes were recorded for asynchronous viewing by students who did not attend in person that week. The remaining lecture content was posted online via instructor‐produced video lectures, outside videos or animations, and online homework. For lab sessions, half of the students attended in‐person each week, and the other half were assigned activities to complete remotely, such as PhysioEx lab simulations, online documentary videos, or low‐tech hands‐on activities that could be completed at home. In the 8th week of the semester, students were surveyed about use of course resources and attitudes about the course and the fall semester in general. A high percentage of survey respondents reported that they “frequently” accessed recordings of live class sessions (14/20 respondents) and online‐only video lectures (17/21 respondents). Technology issues such as slow internet or device incompatibility were reported by 57% of respondents. In response to open‐ended questions about positives and negatives of the course structure, examples of positives included accessibility of class recordings and other materials, flexibility, and “COVID‐friendly”. The majority of negative comments about the course structure involved a general dislike of online learning. The course grade distribution was within the range of grade distributions from prior offerings of the course by the same instructor, suggesting that student learning was not significantly impaired by the change in course structure, although negative impacts on individual students cannot be ruled out. Course structure‐related comments on university student evaluation forms included “easy to maintain studies during quarantine” and “I actually really enjoyed the format”. In conclusion, the hybrid format for this course was generally well‐received by this group of upper‐division biology majors and represents a viable strategy for adapting a biology majors course to the COVID‐19 pandemic.