Undergraduate and graduate teaching assistants (TAs) are tasked with instructing undergraduate courses with little to no professional development (PD). To better develop PD opportunities, it is important to understand the benefits of improving TAs' self-efficacy and the stressors associated with their roles. This study investigated how stress related to the COVID-19 disruption of the spring 2020 semester affected TAs' self-efficacy. Pre-, mid-, and postsemester surveys of self-efficacy and perceived stress were analyzed along with a structured postsemester interview addressing TAs' stress related to the disruption. Although no relationships were found between self-efficacy and stress, qualitative results indicated that stressors related to changes in and uncertainty around their responsibilities influenced TAs' confidence in their teaching. The results of this study are discussed in relation to PD programs providing experiences with multiple teaching modalities, strategies for time management, and mental health resources.